Microbial immunomodulators - abstract. Antitumor immunity Immunostimulating drugs Pharmacology

Orenburg State Agrarian University

Department of Microbiology

Abstract on the topic:

"Microbial immunomodulators"

Orenburg, 2010

1. Immunity and immune system.

2. Immunomodulators

1. Immunity and immune system.

Immunity is the protection of the organism from genetically alien agents of exogenous and endogenous origin, aimed at preserving and maintaining the genetic homeostasis of the organism, its structural, functional, biochemical integrity and antigenic individuality. Immunity is one of the most important characteristics for all living organisms created in the process of evolution. The principle of operation of defense mechanisms is the recognition, processing and elimination of foreign structures. Protection is carried out using two systems - nonspecific (innate, natural) and specific (acquired) immunity. These two systems represent two stages of a single process of protecting the body. Nonspecific immunity acts as the first line of defense and as its final stage, and the acquired immunity system performs intermediate functions of specific recognition and memory of a foreign agent and the activation of powerful innate immunity tools at the final stage of the process. The innate immune system operates on the basis of inflammation and phagocytosis, as well as protective proteins (complement, interferons, fibronectin, etc.). This system reacts only to corpuscular agents (microorganisms, foreign cells, etc.) and toxic substances that destroy cells and tissues, or rather , on the corpuscular products of this destruction. The second and most complex system - acquired immunity - is based on the specific functions of lymphocytes, blood cells that recognize foreign macromolecules and react to them either directly or by producing protective protein molecules (antibodies).

In addition to somatic and infectious diseases, which are widespread among people, the human body is adversely affected by social (insufficient and irrational nutrition, housing conditions, occupational hazards), environmental factors, medical measures (surgical interventions, stress, etc.), in which First of all, the immune system suffers, secondary immunodeficiencies occur. Despite the constant improvement of the methods and tactics of the ongoing basic therapy of diseases and the use of deep reserve drugs involving non-drug methods of influence, the effectiveness of treatment remains at a rather low level. Often the cause of these features in the development, course and outcome of diseases is the presence in patients of certain disorders of the immune system. Research carried out in last years in many countries of the world, have made it possible to develop and introduce into wide clinical practice new integrated approaches to the treatment and prevention of various nosological forms of diseases using targeted immunotropic drugs, taking into account the level and degree of disorders in the immune system. An important aspect in the prevention of relapses and the treatment of diseases, as well as in the prevention of immunodeficiencies, is the combination of basic therapy with rational immunocorrection. Currently, one of the urgent tasks of immunopharmacology is the development of new drugs that combine such important characteristics as efficiency and safety of use.

2. Immunomodulators

Immunomodulators- These are drugs that, when used in therapeutic doses, restore the functions of the immune system (effective immune protection).

Immunomodulators (immunocorrectors) - a group of drugs of biological (drugs from animal organs, plant materials), microbiological and synthetic origin, with the ability to normalize immune responses.

2.1. Clinical application of immunomodulators.

The most reasonable use of immunomodulators seems to be in immunodeficiencies, manifested by increased infectious morbidity. The main target of immunomodulatory drugs are secondary immunodeficiencies, which are manifested by frequent recurrent, difficult-to-treat infectious and inflammatory diseases of all localizations and any etiology. At the heart of every chronic infectious disease inflammatory process lie changes in the immune system, which are one of the reasons for the persistence of this process. The study of the parameters of the immune system can not always reveal these changes. Therefore, in the presence of a chronic infectious and inflammatory process, immunomodulatory drugs can be prescribed even if the immunodiagnostic study does not reveal significant deviations in the immune status.

As a rule, in such processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungal, antiviral or other chemotherapy drugs. According to experts, in all cases when antimicrobial agents are used for secondary immunological deficiency, it is advisable to prescribe immunomodulatory drugs.

The main requirements for immunotropic drugs are:

Immunomodulatory properties;
high efficiency;
natural origin;
safety, harmlessness;
no contraindications;
lack of addiction;
no side effects;
no carcinogenic effects;
lack of induction of immunopathological reactions;
do not cause excessive sensitization and do not potentiate it with other medicines;
easily metabolized and excreted from the body;
do not interact with other drugs and
have high compatibility with them;
non-parenteral routes of administration.

At present, the main principles of immunotherapy have been developed and approved:

1. Mandatory determination of the immune status before the start of immunotherapy;
2. Determining the level and degree of damage to the immune system;
3. Monitoring the dynamics of the immune status in the process of immunotherapy;
4. The use of immunomodulators only in the presence of characteristic clinical signs and changes in immune status indicators
5. Appointment of immunomodulators for preventive purposes to maintain the immune status (oncology, surgical interventions, stress, environmental, professional and other impacts)

Currently, 6 main groups of immunomodulators are distinguished by origin:

Microbial immunomodulators;

Thymic immunomodulators;
bone marrow immunomodulators;
cytokines;
nucleic acids;
chemically pure.

3. Immunomodulators of microbial origin

Immunomodulators of microbial origin can be conditionally divided into three generations. The first drug approved for medical use as an immunostimulant, there was a BCG vaccine, which has a pronounced ability to enhance factors of both innate and acquired immunity.

The microbial preparations of the first generation include such drugs as pyrogenal and prodigiosan, which are polysaccharides of bacterial origin.

Currently, due to pyrogenicity and other side effects they are rarely used.

Microbial preparations of the second generation include lysates (Bronchomunal, IPC-19, Imudon, a Swiss-made Broncho-Vaxom, which has recently appeared on the Russian pharmaceutical market) and ribosomes (Ribomunil) of bacteria, which are mainly among pathogens. respiratory infections Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influezae, etc. These drugs have a dual purpose specific (vaccinating) and nonspecific (immunostimulating).

Likopid, which can be attributed to microbial preparations of the third generation, consists of a natural disaccharide - glucosaminylmuramil and a synthetic dipeptide attached to it - L-alanyl-D-isoglutamine. In the body, the main target for immunomodulators microbial origin are phagocytic cells. Under the influence of these drugs, the functional properties of phagocytes are enhanced (phagocytosis and intracellular killing of absorbed bacteria increase), the production of anti-inflammatory cytokines, necessary for the initiation of humoral and cellular immunity, increases. As a result, the production of antibodies may increase, the formation of antigen-specific T-helpers and T-killers may be activated.

3.1. Preparations of microbial origin.

Bifiform, bifidumbacterin, probifor, linex, acipol, kipacid, enterol, bactisubtil, bifikol, gastrofarm, acilact, bronchomunal, BCG, imudon, IRS-19, sodium nucleinate, prodigiosan, ribomunil, ruzam

Table 4The main immunomodulators of microbial origin, approved for use in Russia

For more than half a century, the immunomodulatory role of Mycobacterium tuberculosis has been known. The BCG vaccine currently has no independent value as an immunomodulator. The only exception is cancer immunotherapy. Bladder, with the use of the BCG-Imuron vaccine. The BCG-Imuron vaccine is a live lyophilized bacteria of the BCG-1 vaccine strain. The drug is used as an instillation into the bladder.

Live mycobacteria, multiplying intracellularly, lead to nonspecific stimulation of the cellular immune response. BCG-Imuron is intended for the prevention of recurrence of superficial bladder cancer after prompt removal tumors, as well as for the treatment of small tumors of the bladder, the removal of which is impossible.

Study of the mechanism of immunomodulatory action BCG vaccines. showed that it is reproduced with the help of the inner layer of the cell wall of Mycobacterium tuberculosis - peptidoglycan, and in the composition of peptidoglycan the active principle is muramyl dipeptide, which is part of the peptidoglycan of the cell wall of almost all known gram-positive and gram-negative bacteria. However, due to high pyrogenicity and other undesirable side effects, muramyl dipeptide itself turned out to be unsuitable for clinical use. Therefore, the search for its structural analogues began.

This is how the drug Licopid (glucosaminylmuramyl dipeptide) appeared, which, along with low pyrogenicity, has a higher immunomodulatory potential.

Licopid has an immunomodulatory effect primarily due to the activation of cells of the phagocytic system of immunity (neutrophils and macrophages). The latter, by phagocytosis, destroy pathogenic microorganisms and, at the same time, secrete mediators of natural immunity - cytokines (interleukin-1, tumor necrosis factor, colony-stimulating factor, gamma interferon), which, acting on a wide range of target cells, cause further development defensive response of the body. Ultimately, Likopid affects all three main links of immunity: phagocytosis, cellular and humoral immunity, stimulates leukopoiesis and regenerative processes.

The main indications for the appointment of Likopid: chronic non-specific lung disease, both in the stage of exacerbation and remission; acute and chronic purulent-inflammatory processes (postoperative, post-traumatic, wound), trophic ulcers; tuberculosis; acute and chronic viral infections, especially genital and labial herpes, herpetic keratitis and keratouveitis, herpes zoster, cytomegalovirus infection; lesions of the cervix caused by the human papillomavirus; bacterial and candidal vaginitis; urogenital infections.

The advantage of licopide is its ability to be used in pediatrics, including neonatology. Likopid is used in the treatment of bacterial pneumonia in term and premature infants. Licopid is used in the complex treatment of chronic viral hepatitis in children. Since Licopid is able to stimulate the maturation of glucuronyltransferase in the liver of newborns, its effectiveness is being tested in conjugated hyperbilirubinemia in the neonatal period.

Microorganisms from exopolysaccharides of various composition microbial origin, as well as mucin produced ... and teichoic acids, known polyclonal inducers immunomodulators. Study of the anti-infective and immunostimulatory activity of L. ...

Immunomodulators - group pharmacological preparations that activate the body's immunological defenses at the cellular or humoral level. These drugs stimulate the immune system and increase the body's nonspecific resistance.

major organs of the human immune system

Immunity is a unique system of the human body that can destroy foreign substances and needs proper correction. Normally, immunocompetent cells are produced in response to the introduction of pathogenic biological agents into the body - viruses, microbes and other infectious agents. Immunodeficiency states are characterized by reduced production of these cells and are manifested by frequent morbidity. Immunomodulators are special preparations, united by a common name and a similar mechanism of action, used to prevent various ailments and strengthen the immune system.

Currently, the pharmacological industry produces a huge number of drugs that have immunostimulating, immunomodulating, immunocorrective and immunosuppressive effects. They are freely sold in the pharmacy chain. Most of them have side effects and have a negative effect on the body. Before purchasing such medicines, you should consult with your doctor.

• Immunostimulants strengthen human immunity, ensure more efficient functioning of the immune system and provoke the production of protective cellular links. Immunostimulants are harmless to people who do not have immune system disorders and exacerbations of chronic pathologies.
• Immunomodulators correct the balance of immunocompetent cells in autoimmune diseases and balance all components of the immune system, suppressing or increasing their activity.
• Immunocorrectors affect only certain structures of the immune system, normalizing their activity.
• Immunosuppressants suppress the production of immunity links in cases where its hyperactivity harms the human body.

Self-medication and inadequate intake of drugs can lead to the development of autoimmune pathology, while the body begins to perceive its own cells as foreign and fight them. Immunostimulants should be taken according to strict indications and as prescribed by the attending physician. This is especially true for children, because their immune system is fully formed only by the age of 14.

But in some cases, it is simply impossible to do without taking drugs of this group. In severe diseases with a high risk of developing serious complications, taking immunostimulants is justified even in babies and pregnant women. Most immunomodulators are low-toxic and quite effective.

The use of immunostimulants

Preliminary immunocorrection is aimed at eliminating the underlying pathology without the use of basic therapy drugs. It is prescribed for people with kidney disease, digestive system, rheumatism, in preparation for surgical interventions.

Diseases in which immunostimulants are used:

1. congenital immunodeficiency,
2. malignant neoplasms,
3. Inflammation of viral and bacterial etiology,
4. Mycoses and protozooses,
5. Helminthiasis,
6. Renal and hepatic pathology,
7. Endocrinopathy - diabetes and other metabolic disorders
8. Immunosuppression while taking some medicines- cytostatics, glucocorticosteroids, NSAIDs, antibiotics, antidepressants, anticoagulants,
9. Immunodeficiency due to ionizing radiation, excessive alcohol intake, severe stress,
10. Allergy,
11. Conditions after transplantation,
12. Secondary post-traumatic and post-intoxication immunodeficiency states.

The presence of signs of immune deficiency is an absolute indication for the use of immunostimulants in children. The best immunomodulator for children can only be selected by a pediatrician.

People who are most often prescribed immunomodulators:

• Children with weak immunity
• Elderly people with depleted immune systems
• People with busy lifestyles.

Treatment with immunomodulators should be under the supervision of a physician and an immunological blood test.

Classification

The list of modern immunomodulators today is very large. Depending on the origin, immunostimulants are isolated:

Self-administration of immunostimulants is rarely justified. Usually they are used as an adjunct to the main treatment of pathology. The choice of drug is determined by the characteristics of immunological disorders in the patient's body. The effectiveness of drugs is considered maximum during an exacerbation of the pathology. The duration of therapy usually varies from 1 to 9 months. The use of adequate doses of the drug and proper adherence to the treatment regimen allows immunostimulants to fully realize their therapeutic effects.

Some probiotics, cytostatics, hormones, vitamins also have an immunomodulatory effect. antibacterial drugs, immunoglobulins.

Synthetic immunostimulants

Synthetic adaptogens have an immunostimulatory effect on the body and increase its resistance to adverse factors. The main representatives of this group are "Dibazol" and "Bemitil". Due to the pronounced immunostimulating activity, the drugs have an anti-asthenic effect and help the body recover quickly after a long stay in extreme conditions.

With frequent and protracted infections, for prophylactic and therapeutic purposes, Dibazol is combined with Levamisole or Decamevit.

Endogenous immunostimulants

This group includes preparations of thymus, red bone marrow and placenta.

Thymic peptides are produced by thymus cells and regulate the immune system. They change the functions of T-lymphocytes and restore the balance of their subpopulations. After the use of endogenous immunostimulants, the number of cells in the blood is normalized, which indicates their pronounced immunomodulatory effect. Endogenous immunostimulants enhance the production of interferons and increase the activity of immunocompetent cells.

• Timalin has an immunomodulatory effect, activates regeneration and reparation processes. It stimulates cellular immunity and phagocytosis, normalizes the number of lymphocytes, increases the secretion of interferons, and restores immunological reactivity. This drug is used to treat immunodeficiency conditions that have developed against the background of acute and chronic infections, destructive processes.
• "Imunofan"- a drug widely used in cases where the human immune system cannot independently resist the disease and requires pharmacological support. It stimulates the immune system, removes toxins and free radicals from the body, and has a hepatoprotective effect.

Interferons

Interferons increase the nonspecific resistance of the human body and protect it from viral, bacterial or other antigenic attacks. Most effective drugs that have a similar effect are "Cycloferon", "Viferon", "Anaferon", "Arbidol". They contain synthesized proteins that push the body to produce its own interferons.

Natural medicines include leukocyte human interferon.

Long-term use of drugs in this group minimizes their effectiveness, inhibits a person's own immunity, which ceases to function actively. Inadequate and too prolonged use of them has a negative impact on the immunity of adults and children.

In combination with other drugs, interferons are prescribed to patients with viral infections, laryngeal papillomatosis, and cancer. They are used intranasally, orally, intramuscularly and intravenously.

Preparations of microbial origin

Medicines of this group have a direct effect on the monocyte-macrophage system. Activated blood cells begin to produce cytokines that trigger innate and adaptive immune responses. The main task of these drugs is to remove pathogenic microbes from the body.

Herbal adaptogens

Herbal adaptogens include extracts of echinacea, eleutherococcus, ginseng, lemongrass. These are "soft" immunostimulants widely used in clinical practice. Preparations from this group are prescribed to patients with immunodeficiency without a preliminary immunological examination. Adaptogens start the work of enzyme systems and biosynthetic processes, activate the nonspecific resistance of the organism.

The use of plant adaptogens for prophylactic purposes reduces the incidence of acute respiratory viral infections and, resists the development of radiation sickness, weakens the toxic effect of cytostatics.

For the prevention of a number of diseases, as well as for a speedy recovery, patients are recommended to drink ginger tea or cinnamon tea daily, take black peppercorns.

Video: about immunity - School of Dr. Komarovsky

The problem of immunotherapy is of interest to doctors of almost all specialties due to the steady growth of infectious and inflammatory diseases that are prone to chronic and recurrent course against the background of the low effectiveness of basic therapy, malignant neoplasms, autoimmune and allergic diseases, systemic diseases, viral infections that cause high level morbidity, mortality and disability. In addition to somatic and infectious diseases, which are widespread among people, the human body is adversely affected by social (insufficient and irrational nutrition, housing conditions, occupational hazards), environmental factors, medical measures (surgical interventions, stress, etc.), in which First of all, the immune system suffers, secondary immunodeficiencies occur. Despite the constant improvement of the methods and tactics of the ongoing basic therapy of diseases and the use of deep reserve drugs involving non-drug methods of influence, the effectiveness of treatment remains at a rather low level. Often the cause of these features in the development, course and outcome of diseases is the presence in patients of certain disorders of the immune system. Studies conducted in recent years in many countries around the world have made it possible to develop and introduce into wide clinical practice new integrated approaches to the treatment and prevention of various nosological forms of diseases using targeted immunotropic drugs, taking into account the level and degree of disorders in the immune system. An important aspect in the prevention of relapses and the treatment of diseases, as well as in the prevention of immunodeficiencies, is the combination of basic therapy with rational immunocorrection. Currently, one of the urgent tasks of immunopharmacology is the development of new drugs that combine such important characteristics as efficiency and safety of use.

Immunity and immune system. Immunity- protection of the organism from genetically alien agents of exogenous and endogenous origin, aimed at preserving and maintaining the genetic homeostasis of the organism, its structural, functional, biochemical integrity and antigenic individuality. Immunity is one of the most important characteristics for all living organisms created in the process of evolution. The principle of operation of defense mechanisms is the recognition, processing and elimination of foreign structures.

Protection is carried out using two systems - nonspecific (innate, natural) and specific (acquired) immunity. These two systems represent two stages of a single process of protecting the body. Nonspecific immunity acts as the first line of defense and as its final stage, and the acquired immunity system performs intermediate functions of specific recognition and memory of a foreign agent and the activation of powerful innate immunity tools at the final stage of the process. The innate immune system operates on the basis of inflammation and phagocytosis, as well as protective proteins (complement, interferons, fibronectin, etc.). This system reacts only to corpuscular agents (microorganisms, foreign cells, etc.) and toxic substances that destroy cells and tissues, or rather , on the corpuscular products of this destruction. The second and most complex system - acquired immunity - is based on the specific functions of lymphocytes, blood cells that recognize foreign macromolecules and react to them either directly or by producing protective protein molecules (antibodies).

Immunomodulators - These are drugs that, when used in therapeutic doses, restore the functions of the immune system (effective immune protection).

Immunomodulators (immunocorrectors) - a group of drugs of biological (drugs from animal organs, plant materials), microbiological and synthetic origin, with the ability to normalize immune responses.

Currently, 6 main groups of immunomodulators are distinguished by origin:

Immunomodulators of microbial origin can be conditionally divided into three generations. The first drug approved for medical use as an immunostimulant was the BCG vaccine, which has a pronounced ability to enhance factors of both innate and acquired immunity.

The microbial preparations of the first generation include such drugs as pyrogenal and prodigiosan, which are polysaccharides of bacterial origin. Currently, due to pyrogenicity and other side effects, they are rarely used.

Microbial preparations of the second generation include lysates (Bronchomunal, IPC-19, Imudon, a Swiss-made Broncho-Vaxom, which has recently appeared on the Russian pharmaceutical market) and ribosomes (Ribomunil) of bacteria, which are mainly among the causative agents of respiratory infections. Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and others. These drugs have a dual purpose specific (vaccinating) and nonspecific (immunostimulating).

Likopid, which can be attributed to microbial preparations of the third generation, consists of a natural disaccharide - glucosaminylmuramil and a synthetic dipeptide attached to it - L-alanyl-D-isoglutamine.

Taktivin, which is a complex of peptides extracted from bovine thymus, became the founder of the first generation thymic preparations in Russia. Preparations containing a complex of thymic peptides also include Timalin, Timoptin, and others, and those containing thymus extracts include Timomulin and Vilozen.

The clinical efficacy of first-generation thymic preparations is not in doubt, but they have one drawback - they are an undivided mixture of biologically active peptides that are rather difficult to standardize.

Progress in the field of drugs of thymic origin went along the line of creating drugs of the II and III generations - synthetic analogues of natural thymus hormones or fragments of these hormones with biological activity. The last direction turned out to be the most productive. On the basis of one of the fragments, including the amino acid residues of the thymopoietin active center, a synthetic hexapeptide Immunofan was created.

The ancestor of drugs of bone marrow origin is Myelopid, which includes a complex of bioregulatory peptide mediators - myelopeptides (MP). It was found that different MPs affect different parts of the immune system: some increase the functional activity of T-helpers; others suppress the proliferation of malignant cells and significantly reduce the ability of tumor cells to produce toxic substances; others stimulate the phagocytic activity of leukocytes.

The regulation of the developed immune response is carried out by cytokines - a complex complex of endogenous immunoregulatory molecules, which are still the basis for creating a large group of both natural and recombinant immunomodulatory drugs. The first group includes Leukinferon and Superlymph, the second - Beta-leukin, Roncoleukin and Leykomax (molgramostim).

The group of chemically pure immunomodulators can be divided into two subgroups: low molecular weight and high molecular weight. The former include a number of well-known drugs that additionally have immunotropic activity.

Their ancestor was levamisole (Decaris) - phenylimidothiazole, a well-known antihelminthic agent, which subsequently showed pronounced immunostimulating properties. Another promising drug from the subgroup of low molecular weight immunomodulators is Galavit, a phthalhydrazide derivative. The peculiarity of this drug is the presence of not only immunomodulatory, but also pronounced anti-inflammatory properties. The subgroup of low molecular weight immunomodulators also includes three synthetic oligopeptides: Gepon, Glutoxim and Alloferon.

High-molecular, chemically pure immunomodulators obtained by targeted chemical synthesis include the drug Polyoxidonium. It is an N-oxidized derivative of polyethylenepiperazine with a molecular weight of about 100 kD. The drug has a wide range of pharmacological effects on the body: immunomodulatory, detoxifying, antioxidant and membrane-protective.

Interferons and interferon inducers should be attributed to drugs characterized by pronounced immunomodulatory properties. Interferons as an integral part of the overall cytokine network of the body are immunoregulatory molecules that have an effect on all cells of the immune system.???

Pharmacological action of immunomodulators.

Immunomodulators of microbial origin .

In the body, the main target for immunomodulators of microbial origin are phagocytic cells. Under the influence of these drugs, the functional properties of phagocytes are enhanced (phagocytosis and intracellular killing of absorbed bacteria increase), the production of pro-inflammatory cytokines, necessary for the initiation of humoral and cellular immunity, increases. As a result, the production of antibodies may increase, the formation of antigen-specific T-helpers and T-killers may be activated.

Immunomodulators of thymic origin.

Naturally, in accordance with the name, the main target for immunomodulators of thymic origin are T-lymphocytes. With initially low levels, drugs of this series increase the number of T-cells and their functional activity. The pharmacological action of the synthetic thymus dipeptide Thymogen is to increase the level of cyclic nucleotides, similar to the effect of the thymus hormone thymopoietin, which leads to stimulation of the differentiation and proliferation of T-cell precursors into mature lymphocytes.

Immunomodulators of bone marrow origin.

The immunomodulators obtained from the bone marrow of mammals (pigs or calves) include Myelopid. Myelopid contains six bone marrow-specific immune response mediators called myelopeptides (MPs). These substances have the ability to stimulate various parts of the immune response, especially humoral immunity. Each myelopeptide has a specific biological action, the combination of which determines its clinical effect. MP-1 restores the normal balance of T-helper and T-suppressor activity. MP-2 inhibits the proliferation of malignant cells and significantly reduces the ability of tumor cells to produce toxic substances that inhibit the functional activity of T-lymphocytes. MP-3 stimulates the activity of the phagocytic link of immunity and, consequently, increases anti-infective immunity. MP-4 affects the differentiation of hematopoietic cells, contributing to their faster maturation, i.e., it has a leukopoietic effect. . In immunodeficiency states, the drug restores the parameters of the B- and T-systems of immunity, stimulates the production of antibodies and the functional activity of immunocompetent cells, and helps to restore a number of other indicators of the humoral immunity link.

Cytokines.

Cytokines are low molecular weight hormone-like biomolecules produced by activated immunocompetent cells and are regulators of intercellular interactions. There are several groups of them - interleukins, growth factors (epidermal, nerve growth factor), colony-stimulating factors, chemotactic factors, tumor necrosis factor. Interleukins are the main participants in the development of the immune response to the invasion of microorganisms, the formation of an inflammatory response, the implementation of antitumor immunity, etc.

Chemically pure immunomodulators

The mechanisms of action of these drugs are best seen using Polyoxidonium as an example. This high molecular weight immunomodulator is characterized by a wide range pharmacological action on the body, including immunomodulatory, antioxidant, detoxifying and membrane-protective effects.

Interferons and interferon inductors.

Interferons are protective substances of a protein nature that are produced by cells in response to the penetration of viruses, as well as to the effects of a number of other natural or synthetic compounds (interferon inducers).

Interferons are factors of non-specific defense of the body against viruses, bacteria, chlamydia, pathogenic fungi, tumor cells, but at the same time they can act as regulators of intercellular interactions in the immune system. From this position, they belong to the immunomodulators of endogenous origin.

Three types of human interferons have been identified: a-interferon (leukocyte), b-interferon (fibroblast) and g-interferon (immune). g-Interferon has less antiviral activity, but plays a more important immunoregulatory role. Schematically, the mechanism of action of interferon can be represented as follows: interferons bind to a specific receptor in the cell, which leads to the synthesis of about thirty proteins by the cell, which provide the above effects of interferon. In particular, regulatory peptides are synthesized that prevent the penetration of the virus into the cell, the synthesis of new viruses in the cell, and stimulate the activity of cytotoxic T-lymphocytes and macrophages.

In Russia, the history of the creation of interferon preparations begins in 1967, when human leukocyte interferon was first created and introduced into clinical practice for the prevention and treatment of influenza and SARS. At present, several modern preparations of alpha-interferon are being produced in Russia, which, according to the production technology, are divided into natural and recombinant ones.

Interferon inducers are synthetic immunomodulators. Interferon inductors are a heterogeneous family of high- and low-molecular synthetic and natural compounds, united by the ability to cause the body to form its own (endogenous) interferon. Interferon inductors have antiviral, immunomodulatory and other effects characteristic of interferon.

Poludan (a complex of polyadenylic and polyuridic acids) is one of the very first interferon inducers, used since the 70s. Its interferon-inducing activity is low. Poludan is used in the form of eye drops and injections under the conjunctiva for herpetic keratitis and keratoconjunctivitis, as well as in the form of applications for herpetic vulvovaginitis and colpitis.

Amiksin is a low molecular weight interferon inducer belonging to the class of fluoreons. Amiksin stimulates the formation in the body of all types of interferons: a, b and g. The maximum level of interferon in the blood is reached approximately 24 hours after taking Amiksin, increasing tenfold compared to its initial values.

An important feature of Amiksin is the long-term circulation (up to 8 weeks) of the therapeutic concentration of interferon after a course of taking the drug. Significant and prolonged stimulation by Amiksin of the production of endogenous interferon provides its universally wide range of antiviral activity. Amiksin also stimulates the humoral immune response, increasing the production of IgM and IgG, and restores the T-helper/T-suppressor ratio. Amiksin is used for the prevention of influenza and other acute respiratory viral infections, the treatment of severe forms of influenza, acute and chronic hepatitis B and C, recurrent genital herpes, cytomegalovirus infection, chlamydia, multiple sclerosis.

Neovir is a low molecular weight interferon inducer (derivative of carboxymethylacridone). Neovir induces high titers of endogenous interferons in the body, especially early interferon alpha. The drug has immunomodulatory, antiviral and antitumor activity. Neovir is used for viral hepatitis B and C, as well as for urethritis, cervicitis, salpingitis of chlamydial etiology, viral encephalitis.

Clinical application of immunomodulators.

The most reasonable use of immunomodulators seems to be in immunodeficiencies, manifested by increased infectious morbidity. The main target of immunomodulatory drugs are secondary immunodeficiencies, which are manifested by frequent recurrent, difficult-to-treat infectious and inflammatory diseases of all localizations and any etiology. At the heart of each chronic infectious and inflammatory process are changes in the immune system, which are one of the reasons for the persistence of this process. The study of the parameters of the immune system can not always reveal these changes. Therefore, in the presence of a chronic infectious and inflammatory process, immunomodulatory drugs can be prescribed even if the immunodiagnostic study does not reveal significant deviations in the immune status.

As a rule, in such processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungal, antiviral or other chemotherapy drugs. According to experts, in all cases when antimicrobial agents are used for secondary immunological deficiency, it is advisable to prescribe immunomodulatory drugs.

Basic requirements requirements for immunotropic drugs are:

immunomodulatory properties; high efficiency; natural origin; safety, harmlessness; no contraindications; lack of addiction; no side effects; no carcinogenic effects; lack of induction of immunopathological reactions; do not cause excessive sensitization and do not potentiate it with other medicines; easily metabolized and excreted from the body; do not interact with other drugs and have high compatibility with them; non-parenteral routes of administration.

At present, the main principles of immunotherapy:

1. Mandatory determination of the immune status before the start of immunotherapy;

2. Determining the level and degree of damage to the immune system;

3. Monitoring the dynamics of the immune status in the process of immunotherapy;

4. The use of immunomodulators only in the presence of characteristic clinical signs and changes in the parameters of the immune status

5. Appointment of immunomodulators for preventive purposes to maintain the immune status (oncology, surgical interventions, stress, environmental, professional and other impacts).

Determination of the level and degree of damage to the immune system is one of the most important stages in the selection of a drug for immunomodulatory therapy. The point of application of the action of the drug should correspond to the level of disturbance of the activity of a certain link in the immune system in order to ensure the maximum effectiveness of the therapy.

Let us dwell on the consideration of individual immunomodulators.

Methylphenylthiomethyl-Dimethylaminomethyl-Hydroxybromindole Carboxylic acid ethyl ester.

chemical name.

6-Bromo-5-hydroxy-1-methyl-4-dimethylaminomethyl-2-phenylthiomethylindole-3-carboxylic acid ethyl ester hydrochloride

Gross formula -C 22 H 25 BrlN 2 O 3 S.HCl

Characteristic.

Crystalline powder from white with a greenish tint to light yellow with a greenish tint. Practically insoluble in water.

Pharmacology.

Pharmacological action - antiviral, immunostimulating. It specifically inhibits influenza A and B viruses. The antiviral effect is due to the suppression of the fusion of the lipid envelope of the virus with cell membranes upon contact of the virus with the cell. It exhibits interferon-inducing and immunomodulatory activity, stimulates humoral and cellular immune responses, the phagocytic function of macrophages, and increases the body's resistance to viral infections.

Therapeutic efficacy in influenza is expressed in a decrease in the symptoms of intoxication, the severity of catarrhal phenomena, a shortening of the period of fever and the total duration of the disease. Prevents the development of post-influenza complications, reduces the frequency of exacerbations chronic diseases, normalizes immunological parameters.

When taken orally, it is rapidly absorbed from the gastrointestinal tract and distributed to organs and tissues. C max in the blood at a dose of 50 mg is reached after 1.2 hours, at a dose of 100 mg - after 1.5 hours. T 1/2 ?- about 17? The largest number The drug is found in the liver. It is excreted mainly with faeces.

Application.

Treatment and prevention of influenza and other acute respiratory viral infections (including those complicated by bronchitis and pneumonia); chronic bronchitis, pneumonia, recurrent herpetic infection(in complex treatment); for prevention infectious complications and normalization of the immune status in the postoperative period.

Echinacea.

Latin name -Echinacea.

Characteristic.

Echinacea ( Echinacea Moench)? - a perennial herbaceous plant from the Aster family (Asteraceae)? - Asteraceae (Compositae).

Echinacea purpurea ( Echinacea purpurea(L.) Moench.) and Echinacea pallidum ( Echinacea pallida Nutt.)? - herbaceous plants with a height of 50-100 and 60-90 cm, respectively. Echinacea narrow-leaved ( Echinacea angustifolia DC) has a lower stem, up to 60 cm high.

Herb, rhizomes and roots of echinacea are used as medicinal raw materials in fresh or dried form.

Echinacea purpurea herb contains polysaccharides (heteroxylans, arabinoramnogalactans), essential oils(0.15-0.50%), flavonoids, hydroxycinnamic (chicory, ferulic, coumaric, caffeic) acids, tannins, saponins, polyamines, echinacin (polyunsaturated acid amide), echinolone (unsaturated ketoalcohol), echinacoside (a glycoside containing caffeic acid and catechol), organic acids, resins, phytosterols; rhizomes and roots? - inulin (up to 6%), glucose (7%), essential and fatty oils, phenolcarboxylic acids, betaine, resins. All parts of the plant contain enzymes, macro- (potassium, calcium) and microelements (selenium, cobalt, silver, molybdenum, zinc, manganese, etc.).

In medical practice, tinctures, decoctions and extracts of echinacea are used. On an industrial scale, mainly drugs are produced based on the juice or extract of the herb Echinacea purpurea.

Pharmacology.

Pharmacological action - immunostimulating, anti-inflammatory. Promotes the activation of non-specific factors of body defense and cellular immunity, improves metabolic processes. Stimulates bone marrow hematopoiesis, increases the number of leukocytes and cells of the reticuloendothelial system of the spleen.

It increases the phagocytic activity of macrophages and granulocyte chemotaxis, promotes the release of cytokines, increases the production of interleukin-1 by macrophages, accelerates the transformation of B-lymphocytes into plasma cells, enhances antibody formation and T-helper activity.

Application.

Immunodeficiencies caused by acute infectious diseases (prevention and treatment): colds, influenza, infectious diseases inflammatory diseases nasopharynx and oral cavity. Recurrent infections of the respiratory and urinary tract(as part of complex therapy); as an auxiliary drug for long-term antibiotic treatment: chronic infectious and inflammatory diseases (polyarthritis, prostatitis, gynecological diseases).

Local treatment: long-term non-healing wounds.

Interferon alfa.

Latin name - Interferon alpha*

Pharmacology.

Pharmacological action - antiviral, immunomodulatory, antitumor, antiproliferative. Prevents viral infection of cells, changes the properties of the cell membrane, prevents adhesion and penetration of the virus into the cell. Initiates the synthesis of a number of specific enzymes, disrupts the synthesis of viral RNA and viral proteins in the cell. Changes the cytoskeleton of the cell membrane, metabolism, preventing the proliferation of tumor (especially) cells. It has a modulating effect on the synthesis of certain oncogenes, leading to the normalization of neoplastic cell transformation and inhibition of tumor growth. Stimulates the process of antigen presentation to immunocompetent cells, modulates the activity of killers involved in antiviral immunity. With the / m introduction, the rate of absorption from the injection site is uneven. Time to reach C max in plasma is 4-8 hours. In the systemic circulation, 70% of the administered dose is distributed. T 1/2 ?- 4-12? h (depending on the variability of absorption). It is excreted mainly by the kidneys by glomerular filtration.

Application.

Hairy cell leukemia, chronic myeloid leukemia, viral hepatitis B, viral active hepatitis C, primary (essential) and secondary thrombocytosis, transitional form of chronic granulocytic leukemia and myelofibrosis, multiple myeloma, kidney cancer; AIDS-related Kaposi's sarcoma, mycosis fungoides, reticulosarcoma, multiple sclerosis, prevention and treatment of influenza and acute respiratory viral infection.

Interferon alfa-2a + Benzocaine* + Taurine*.

Latin name -Interferon alfa-2a + Benzocaine* + Taurine*

Characteristic. Combined drug.

Pharmacology.

Pharmacological action - antimicrobial, immunomodulatory, regenerating, local anesthetic. Interferon alpha-2 has antiviral, antimicrobial and immunomodulatory effects; enhances the activity of natural killers, T-helpers, phagocytes, as well as the intensity of differentiation of B-lymphocytes. Activation of leukocytes contained in the mucous membrane ensures their active participation in the elimination of primary pathological foci and ensures the restoration of secretory IgA production. Interferon alpha-2 also directly inhibits the replication and transcription of viruses and chlamydia.

Taurine has regenerative, reparative, membrane and hepatoprotective, antioxidant and anti-inflammatory effects.

Benzocaine?— local anesthetic; reduces the permeability of the cell membrane to Na + . Prevents the occurrence of pain impulses in the endings of sensory nerves and their conduction along the nerve fibers.

With intravaginal and rectal application, interferon alfa-2 is absorbed through the mucous membrane and enters the surrounding tissues, lymphatic system providing systemic action. Due to partial fixation on the cells of the mucous membrane, it has a local effect. A decrease in the serum concentration of interferon alpha-2 is observed 12 hours after administration.

Application.

Infectious and inflammatory diseases of the urogenital tract (as part of complex therapy): genital herpes, chlamydia, ureaplasmosis, mycoplasmosis, recurrent vaginal candidiasis, gardnerellosis, trichomoniasis, papillomavirus infections, bacterial vaginosis, cervical erosion, cervicitis, vulvovaginitis, bartholinitis, adnexitis, prostatitis, urethritis, balanitis, balanoposthitis.

Interferon beta-1a.

Latin name - Interferon beta-1a

Characteristic.

Recombinant human interferon beta-1a produced by mammalian cells (Chinese hamster ovary cell culture). Specific antiviral activity? - more than 200? million? It exists in a glycosylated form, contains 166 amino acid residues and a complex carbohydrate fragment associated with a nitrogen atom. The amino acid sequence is identical to natural (natural) human interferon beta.

Pharmacology.

Pharmacological action - antiviral, immunomodulatory, antiproliferative. It binds to specific receptors on the cell surface of the human body and triggers a complex cascade of intercellular interactions, leading to interferon-mediated expression of numerous gene products and markers, incl. class I histocompatibility complex, protein M X, 2",5"-oligoadenylate synthetases, beta 2 microglobulin and neopterin.

Biological activity markers (neopterin, beta 2 -microglobulin, etc.) are determined in healthy donors and patients after parenteral administration of doses of 15-75? The concentration of these markers increases within 12 hours after administration and remains elevated for 4-7 days. The peak of biological activity in typical cases is observed 48 hours after administration. The exact relationship between plasma levels of interferon beta-1a and the concentration of marker proteins, the synthesis of which it induces, is still unknown.

Stimulates the activity of suppressor cells, enhances the production of interleukin-10 and transforming growth factor beta, which have anti-inflammatory and immunosuppressive effects in multiple sclerosis. Interferon beta-1a significantly reduces the frequency of exacerbations and the rate of progression of irreversible neurological disorders in relapsing-remitting multiple sclerosis (the increase in the number and area of ​​focal brain lesions slows down according to MRI). Treatment may be accompanied by the appearance of antibodies to interferon beta-1a. They decrease his activity. in vitro(neutralizing antibodies) and biological effects (clinical efficacy) in vivo. With a duration of treatment of 2 years, antibodies are found in 8% of patients. According to other data, after 12 months of treatment, antibodies appear in the serum in 15% of patients.

No mutagenic activity was found. Data on the study of carcinogenicity in animals and humans are not available. In a reproductive study in rhesus monkeys treated with interferon beta-1a at doses 100 times higher than the MRHD, ovulation cessation and a decrease in serum progesterone levels were observed in some animals (the effects were reversible). In monkeys treated with doses 2 times the recommended weekly dose, these changes were not detected.

The administration of doses 100 times higher than the MRDC to pregnant monkeys was not accompanied by manifestations of teratogenic effects and a negative effect on fetal development. However, doses 3-5 times the weekly recommended dose caused miscarriage (no miscarriage occurred at 2 times the weekly dose).

Information on the effect on reproductive function in humans is not available.

Pharmacokinetic studies of interferon beta-1a in patients with multiple sclerosis have not been conducted.

In healthy volunteers, pharmacokinetic parameters depended on the route of administration: when administered intramuscularly at a dose of 60? max was 45?IU/ml and was reached in 3-15?h, T 1/2 ?— 10 h; with s / c introduction C max?- 30? IU / ml, time to reach it? - 3-18? h, T 1/2 ?- 8.6? h. Bioavailability with i / m administration was 40%, with s / c? - 3 times lower. There are no data indicating a possible penetration into breast milk.

Application.

Recurrent multiple sclerosis (if there are at least 2 relapses of neurological dysfunction within 3 years and there is no evidence of continuous progression of the disease between relapses).

Sodium oxodihydroacridinyl acetate.

Latin name - Cridanimod*

chemical name - Sodium 10-methylenecarboxylate-9-acridone

Pharmacology.

Pharmacological action - immunomodulatory, antiviral. The immunostimulatory effect is due to the induction of interferon synthesis. Increases the ability of interferon-producing cells to produce interferon upon induction by a pathological agent (the property is preserved long time after discontinuation of the drug) and creates high titers of endogenous interferons in the body, identified as early alpha and beta interferons. Activates bone marrow stem cells, eliminates imbalance in subpopulations of T-lymphocytes with activation of effector links of T-cell immunity and macrophages. Against the background of tumor diseases, it enhances the activity of natural killer cells (due to the production of interleukin-2) and normalizes the synthesis of tumor necrosis factor. Stimulates the activity of polymorphonuclear leukocytes (migration, cytotoxicity, phagocytosis). It has antiviral (in relation to RNA and DNA genomic viruses) and antichlamydial action.

After intramuscular injection bioavailability exceeds 90%. With max in plasma (in the dose range of 100-500 mg) is recorded after 30 minutes and is accompanied by an increase in the concentration of serum interferon (reaches 80-100? IU / ml of plasma at a dose of 250 mg). Easily passes through histohematic barriers. Excreted by the kidneys, more than 98% unchanged, T 1/2 ?— 60 min. The activity of induced interferons after reaching the maximum gradually decreases and reaches the initial values ​​after 46-48 hours.

When administered parenterally to animals various kinds doses 40-50 times higher than the therapeutic doses recommended for humans, no lethal outcomes have been identified. The study of chronic toxicity indicates the absence of a negative effect on the functions of the cardiovascular, nervous, digestive, respiratory, excretory, hematopoietic and other body systems. Mutagenic activity in tests on animals, human cell cultures and bacteria was not detected. Does not have a damaging effect on human germ cells. Embryotoxic and teratogenic effects have not been identified.

Application.

Prevention and treatment of infectious and inflammatory diseases, correction of immunodeficiency states and immunostimulating therapy: SARS, incl. flu (severe forms); herpetic infection (Herpes simplex, Varicella zoster) different localization (severe primary and recurrent forms); viral encephalitis and encephalomyelitis; hepatitis (A, B, C, acute and chronic form, including during convalescence); CMV infection on the background of immunodeficiency; chlamydial, ureaplasma, mycoplasma infection (urethritis, epididymitis, prostatitis, cervicitis, salpingitis, chlamydial lymphogranuloma); candidal and bacterial candidal infections (skin, mucous membranes, internal organs); multiple sclerosis; oncological diseases; immunodeficiency (radiation, acquired and congenital with inhibition of interferon synthesis).

Meglumine acridone acetate.

Latin name - Meglumine acridonacetate.

Characteristic.

Low molecular weight interferon inducer.

Pharmacology.

Pharmacological action - antiviral, immunostimulating, anti-inflammatory. Stimulates the production of alpha, beta and gamma interferons (up to 60-80? U / ml and above) by leukocytes, macrophages, T- and B-lymphocytes, epithelial cells, as well as tissues of the spleen, liver, lungs, brain. Penetrates into the cytoplasm and nuclear structures, induces the synthesis of "early" interferons. Activates T-lymphocytes and natural killer cells, normalizes the balance between subpopulations of T-helpers and T-suppressors. Contributes to the correction of the immune status in immunodeficiency states various genesis, incl.

HIV-conditioned.

Active against viruses tick-borne encephalitis, influenza, hepatitis, herpes, CMV, HIV, various enteroviruses, chlamydia.

Shows high efficiency in rheumatic and other systemic diseases connective tissue, suppressing autoimmune reactions and providing anti-inflammatory and analgesic effects.

Differs in low toxicity and lack of mutagenic, teratogenic, embryotoxic and carcinogenic effects.

When ingested, the maximum allowable dose C max in the blood is reached after 1-2 hours, the concentration gradually decreases after 7 hours, after 24 hours it is found in trace amounts. Passes through the BBB. T 1/2 is 4-5 hours. Does not accumulate with prolonged use.

Application

Solution for injection, tablets:

infections: HIV-caused, cytomegalovirus, herpetic; urogenital, incl. chlamydia, neuroinfections (serous meningitis, tick-borne borreliosis, multiple sclerosis, arachnoiditis, etc.), acute and chronic viral hepatitis (A, B, C, D);

immunodeficiency states of various etiologies (postoperative period, burns, chronic bacterial and fungal infections, including bronchitis, pneumonia); peptic ulcer and duodenum; oncological diseases; rheumatoid arthritis; degenerative-dystrophic diseases of the joints (deforming osteoarthritis, etc.); skin diseases (neurodermatitis, eczema, dermatosis).

Pills: flu and SARS.

Liniment: genital herpes, urethritis and balanoposthitis (nonspecific, candidal, gonorrheal, chlamydial and trichomonas etiology), vaginitis (bacterial, candidal).

Sodium deoxyribonucleate.

Latin name - Sodium deoxyribonucleate

Characteristic.

Transparent colorless liquid (extract from sturgeon milk).

Pharmacology.

Pharmacological action - immunomodulatory, anti-inflammatory, reparative, regenerating. Activates antiviral, antifungal and antimicrobial immunity at the cellular and humoral levels. Regulates hematopoiesis, normalizing the number of leukocytes, granulocytes, phagocytes, lymphocytes and platelets. Corrects the state of tissues and organs in dystrophies of vascular origin, exhibits weak anticoagulant properties.

In patients with chronic ischemic disease of the lower extremities (including against the background of diabetes mellitus), it increases exercise tolerance when walking, reduces pain in calf muscles, prevents the development of a feeling of coldness and chilliness of the feet. Improves blood circulation in the lower extremities, promotes the healing of gangrenous trophic ulcers, the appearance of a pulse in the peripheral arteries. It accelerates the rejection of necrotic masses (for example, on the phalanges of the fingers), which sometimes makes it possible to avoid surgical intervention. In patients with coronary artery disease improves myocardial contractility, improves microcirculation in the heart muscle, increases tolerance to physical activity and shortens recovery time. Stimulates reparative processes in gastric and duodenal ulcers, restores the structure of the mucous membrane, inhibits the growth of Helicobacter pylori. Facilitates engraftment of autografts during skin and eardrum transplantation.

Application.

Solutions for external use and for injections: SARS, trophic ulcers, burns, frostbite, long-term non-healing wounds, incl. in diabetes mellitus, purulent-septic processes, graft surface treatment before and after transplantation. Solution for external use: obliterating diseases of the lower extremities, defects of the mucous membrane of the mouth, nose, vagina. Solution for injection: myelodepression and resistance to cytostatics in cancer patients, acute pharyngeal syndrome, peptic ulcer of the stomach and duodenum, gastroduodenitis, coronary artery disease, cardiovascular insufficiency, chronic ischemic disease of the lower extremities II and III stages, prostatitis, vaginitis, endometritis, infertility and impotence caused by chronic infections, chronic obstructive bronchitis.

Polyoxidonium (Azoximer).

Latin name - Polyoxidonium

chemical name - Copolymer of N-hydroxy-1,4-ethylenepiperazine and (N-carboxy)-1,4-ethylenepiperazinium bromide.

Characteristic.

Lyophilized porous mass with a yellowish tint. Soluble in water, isotonic sodium chloride solution, procaine solution. Hygroscopic. Molecular weight? - 60000-100000.

Pharmacology.

Pharmacological action - immunomodulatory, detoxifying. Increases the body's resistance to infections (local, generalized). Immunomodulation is due to a direct effect on phagocytic cells and natural killers, stimulation of antibody production.

Restores immune responses severe forms immunodeficiencies, incl. in secondary immunodeficiency conditions caused by infections (tuberculosis, etc.), malignant neoplasms, therapy with steroid hormones or cytostatics, complications of surgical operations, injuries and burns.

With sublingual application, polyoxidonium activates lymphoid cells located in the bronchi, nasal cavity, eustachian tubes thereby increasing the resistance of these organs to infectious agents.

At oral administration polyoxidonium activates lymphoid cells located in the intestine, namely B-cells that produce secretory IgA.

The consequence of this is an increase in the resistance of the gastrointestinal tract and respiratory tract to infectious agents. In addition, when administered orally, polyoxidonium activates tissue macrophages, which contributes to faster elimination of the pathogen from the body in the presence of an infection focus.

As part of complex therapy, it increases the effectiveness of antibacterial and antiviral agents, bronchodilators and glucocorticoids. Allows you to reduce the dose of these drugs and reduce the duration of treatment. Increases the resistance of cell membranes to cytotoxic action, reduces the toxicity of drugs. It has a pronounced detoxifying activity (due to the polymeric nature of the drug). Does not possess mitogenic polyclonal activity, antigenic and allergenic properties.

It has a high bioavailability (89%) when administered intramuscularly, Cmax max observed 1 hour after rectal and 40 minutes after intramuscular injection. T 1/2 ?- 30 and 25 minutes with rectal and / m administration? (fast phase), 36.2 h with rectal and intramuscular injection and 25.4 h with i.v. administration (slow phase). It is metabolized in the body and excreted mainly by the kidneys.

Tiloron.

Latin name - Tilorone*

chemical name - 2,7-Bis--9H-fluoren-9-one (and as dihydrochloride)

Gross formula -C 25 H 34 N 2 O 3

Pharmacology.

Pharmacological action - antiviral, immunomodulatory. Induces the formation of interferons (alpha, beta, gamma) by intestinal epithelial cells, hepatocytes, T-lymphocytes and granulocytes. After oral administration, the maximum production of interferon is determined in the sequence intestine? - liver? - blood after 4-24 hours.

It activates bone marrow stem cells, stimulates humoral immunity, increases the production of IgM, IgA, IgG, affects antibody production, reduces the degree of immunosuppression, and restores the T-helper/T-suppressor ratio.

The mechanism of antiviral action is associated with the inhibition of translation of virus-specific proteins in infected cells, as a result of which viral replication is suppressed. Effective against influenza viruses and viruses that cause acute respiratory viral infections, hepato- and herpes viruses, incl. CMV and others.

After oral administration, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is 60%. Plasma protein binding? - about 80%. Does not undergo biotransformation. T 1/2 ?- 48? It is excreted unchanged in faeces (70%) and urine (9%). Does not accumulate.

Application.

In adults: viral hepatitis A, B, C; herpetic and cytomegalovirus infection; as part of the complex therapy of infectious-allergic and viral encephalomyelitis (multiple sclerosis, leukoencephalitis, uveoencephalitis, etc.), urogenital and respiratory chlamydia; treatment and prevention of influenza and SARS.

In children older than 7 years: treatment and prevention of influenza and SARS.

Compound drugs.

Wobenzym.

Pharmacological action - immunomodulatory, anti-inflammatory, decongestant, fibrinolytic, antiplatelet.

Pharmacodynamics.

Wobenzym is a combination of natural plant and animal enzymes. Once in the body, enzymes are absorbed into small intestine by resorption of intact molecules and, by binding to blood transport proteins, enter the bloodstream. In the future, enzymes, migrating along the vascular bed and accumulating in the area of ​​the pathological process, have an immunomodulatory, anti-inflammatory, fibrinolytic, anti-edematous, antiplatelet and secondary analgesic effect.

Wobenzym has a positive effect on the course of the inflammatory process, limits the pathological manifestations of autoimmune and immunocomplex processes, and has a positive effect on the parameters of the body's immunological reactivity. It stimulates and regulates the level of functional activity of monocytes-macrophages, natural killer cells, stimulates antitumor immunity, cytotoxic T-lymphocytes, phagocytic activity of cells.

Under the influence of Wobenzym, the number of circulating immune complexes decreases and the membrane deposits of immune complexes are removed from tissues.

Wobenzym reduces the infiltration of the interstitium by plasma cells. Increases the elimination of protein detritus and fibrin deposits in the area of ​​inflammation, accelerates the lysis of toxic metabolic products and necrotic tissues. Improves resorption of hematomas and edema, normalizes the permeability of vessel walls.
Wobenzym reduces the concentration of thromboxane and platelet aggregation. Regulates the adhesion of blood cells, increases the ability of erythrocytes to change their shape by regulating their plasticity, normalizes the number of normal discocytes and reduces the total number of activated forms of platelets, normalizes blood viscosity, reduces the total number of microaggregates, thus improving microcirculation and rheological properties of blood, as well as supply tissues with oxygen and nutrients.

Wobenzym reduces the severity of side effects associated with taking hormonal drugs (hypercoagulation, etc.).
Wobenzym normalizes lipid metabolism, reduces the synthesis of endogenous cholesterol, increases the content of HDL, reduces the level of atherogenic lipids, improves the absorption of polyunsaturated fatty acids.

Wobenzym increases the concentration of antibiotics in the blood plasma and inflammation, thus increasing the effectiveness of their use. At the same time, enzymes reduce unwanted side effects of antibiotic therapy (immune suppression, allergic manifestations, dysbacteriosis).

Wobenzym regulates nonspecific defense mechanisms (phagocytosis, interferon production, etc.), thereby exhibiting antiviral and antimicrobial effects.

Likopid.

Pharmachologic effect - immunomodulatory.

Pharmacokinetics.

The bioavailability of the drug when taken orally is 7-13%. The degree of binding with blood albumin? - Weak. Does not form active metabolites. T max?— 1.5 h, T 1/2 ?- 4.29 hours. Excreted from the body unchanged, mainly through the kidneys.

Pharmacodynamics.

The biological activity of the drug is due to the presence of specific receptors (NOD-2) to glucosaminylmuramyl dipeptide (GMDP) localized in the endoplasm of phagocytes and T-lymphocytes. The drug stimulates the functional (bactericidal, cytotoxic) activity of phagocytes (neutrophils, macrophages), enhances the proliferation of T- and B-lymphocytes, increases the synthesis of specific antibodies.

Pharmacological action is carried out by increasing the production of interleukins (IL-1, IL-6, IL-12), tumor necrosis factor-alpha, interferon gamma, colony-stimulating factors. The drug increases the activity of natural killer cells.

The current situation and development forecast of the Russian market of immunomodulators can be found in the report of the Academy of Industrial Market Studies "Market of Immunomodulators in Russia".

Academy of Industrial Market Studies

Medicinal substances that activate (restore) the function of the cellular and / or humoral immunity system are called immunostimulants. They are used when primary (congenital, usually of a hereditary nature), and secondary (acquired) caused by various factors, both endogenous (disease) and exogenous (eg, stress, drugs, ionizing radiation).

However positive results obtained mainly in the treatment of diseases accompanied by secondary immunodeficiency. In primary immunodeficiencies, the most promising method of treatment at present is the transplantation of immunocompetent organs and cells (bone marrow, thymus). Secondary immunodeficiencies can develop with many viral (measles, rubella, influenza, mumps, viral hepatitis, HIV infection, etc.), bacterial (leprosy, cholera, syphilis, tuberculosis, etc.), mycotic, protozoal (malaria, toxoplasmosis, trypanosomiasis, leishmaniasis, etc.) diseases and helminthiases. Insufficiency of the immune system was also revealed in tumors of a lymphoreticular nature (reticulosarcoma, lymphogranulomatosis, lymphosarcoma, myeloma, chronic lymphocytic leukemia etc.) and in pathological processes accompanied by a loss of protein or a violation of its metabolism (kidney disease with kidney failure, burn disease, diabetes mellitus and other metabolic diseases, chronic hepatitis, severe surgical trauma etc.). Immunosuppression can be caused by drugs (cytostatics, glucocorticosteroids, NSAIDs, antibiotics, ALG, ATH, monoclonal antibodies; CNS depressants, anticoagulants, etc.), as well as alcohol, ionizing radiation, pesticides and other exogenous factors. The immaturity of the immune system has been found in newborns and infants. Immunodeficiency states can also occur as a result of aging. Exogenous damaging factors earlier and more intensely affect the T-system of immunity. With a pronounced protein deficiency, the B-system predominantly suffers. Old age is a pronounced T-immunodeficiency.

Classification. Immunostimulants include drugs of various pharmacological groups, biogenic substances, heterogeneous in chemical structure. Origin they can be classified as follows:

1. Endogenous compounds and their synthetic analogues:

Preparations of thymus (thymalin, vilozen, imunofan, thymogen), red bone marrow (myelopid), placenta (placenta extract)

Immunoglobulins - normal human immunoglobulin (immunovenin, izgam, etc.); human antistaphylococcal immunoglobulin, human anticytomegalovirus immunoglobulin (cytotect), etc.;

Interferons - recombinant interferon-γ (gammaferon, immunoferon)

Interleukins - recombinant interleukin-1β (betaleukin), recombinant interleukin-2β (proleukin)

Growth factors - recombinant human granulocyte-macrophage colony-stimulating factor (molgramostim)

Regulatory peptides - dalargin.

2. bacterial origin and their analogues: vaccines (BCG and others), extracts (Biostom), lysates (bronchomunal, Imudon), cell wall lipopolysaccharide (pyrogenal, prodigiosan, lycopida), a combination of ribosomes and cell wall fractions (Ribomunil), fungal (bestatin, etc.) and yeast polysaccharides (zymosan), probiotics (linex, blasten).

3. Synthetic: purine and pyrimidine (methyluracil, pentoxyl, etc.), imidazole derivatives (dibazole), interferon inducers (cycloferon, amixin), etc.

4. vegetable origin and their analogs: adaptogens (preparations of echinacea (immunal), eleutherococcus, ginseng, Rhodiola rosea), others (aloe, garlic, beans, onions, red pepper, etc.).

5. Other classes: preparations of vitamins C, A, E; metals (zinc, copper, etc.).

Pharmacodynamics. The mechanism of action of immunostimulation of all known drugs is poorly understood. All immunomodulators cause total stimulation of the immune system. However, a certain selectivity in the action of various immunostimulants on various components and stages of the immune response has recently been revealed: macrophages, T- and B-lymphocytes, their subpopulations, natural killers, etc. Therefore, according to the mechanism of action, immunostimulants are classified into drugs, predominantly stimulate:

1. Non-specific protective factors: anabolic agents - steroid (retabolil, phenobolil), non-steroidal (methyluracil, pentoxyl), preparations of vitamins A, E, C, vegetable;

2. Monocytes (macrophages): sodium nucleinate, zymosan, vaccines (BCG, etc.), Pyrogenal, prodigiosan, Biostom;

3. T-lymphocytes: dibazol, thymalin, taktivin, thymogen, zinc preparations, Leukin interval (IL-2), etc.;

4. B-lymphocytes: myelopid, dalargin, bestatin, amastatin, etc.;

5. NK and K cells: interferons, antiviral drugs (isoprinosine), placenta extract, etc.

These data create a fundamental opportunity for their more differentiated application, focused on the modulation of individual links of immunity. At the same time, such selectivity of the action of immunostimulants and a certain selectivity of immunosuppressors create theoretical prerequisites for the development of a combination of drugs of both groups, modes of their use (simultaneous or sequential) for adequate targeted correction of immunity both in autoimmune diseases and in immunodeficiency states.

Indications. Experience in the clinical use of immunostimulants is still limited, due to the lack of immunological specificity, pronounced side effects and insufficient efficacy.

The choice of the drug should not occur spontaneously, without taking into account the immunological status of the patient and the characteristics of the immunotropic activity of the catalyst intended. When choosing an immunostimulant, preference is given to preparations of natural origin, which have moderately modulating properties, low toxicity and are effective when administered orally. Given the modulating nature of the effect of immunostimulants, the dose and duration of treatment each time should be determined individually. The effectiveness of immunostimulating therapy is evaluated on the basis of dynamic monitoring of the patient's condition and indicators of cellular, humoral and nonspecific immunity.

The main indications for the use of immunostimulants are:

1. Primary (hereditary) immunodeficiencies;

2. Secondary immunodeficiencies (often T-systems):

1) with viral, bacterial, mycotic, protozoal diseases, helminthiases. Immunostimulation in these cases complements the specific antibiotic therapy. In this case, the choice of immunostimulant should be, as far as possible, targeted, taking into account the nature of immunosuppression and the chemotherapeutic agent used;

2) with tumors of a lymphoreticular nature. Immunostimulants thymosin, thymalin, taktivin, strengthening the T-killer system of immune "surveillance", delay the growth of tumors and their metastasis. At the same time, they enhance the effect of anticancer drugs and eliminate side effects. traditional methods cancer therapy, improve the general condition of patients and increase their life expectancy;

3) when pathological conditions accompanied by hypoproteinemia;

4) when using drugs (immunosuppressants that depress the central nervous system, anticoagulants, etc.), alcohol, ionizing radiation, pesticides;

5) in newborns and children of 1 years of age; when aging.

These indications do not exhaust the therapeutic possibilities of immunomodulatory therapy. During the development of the immune response, nonspecific stimulation of immunity occurs by various agents of endo and exogenous origin. That is why the introduction of similar substances from the outside in the form of drugs will cause a similar effect of stimulation in cases where this is necessary. Nonspecific immunocorrection enhancing an existing induced immune response is known as adjuvant phenomenon (potentiation). Most of the drugs used in clinical practice are able to enhance the immunological reactions caused by thymus-dependent and thymus-independent AH. their high activity is observed with suboptimal antigenic irritation and reduced function of T- and B-links of immunity. They shorten the inductive phase of immunogenesis and prolong immunity.

Thymus preparations and their synthetic analogues ( thymalin , imunofan etc.) Refer to polypeptides that are obtained from cattle, and are functional analogues of natural thymic cytokines, providing humoral regulation proliferation and differentiation of cells of the peripheral immune system of the body. The mechanism of action of these drugs is based on the ability to regulate the processes of proliferation/differentiation of immune cells. The immunostimulating effect is expressed in an adequate change in the functional state of the cells of the T-system of immunity; increased production of a- and γ-interferons. They can stimulate the B-system and the macrophage-monocytic link of immunity, the activity of NK cells. Immunofan is a synthetic thymomimetic, has immunoregulatory, detoxifying, hepatoprotective and antioxidant effects. Normalizes the reactions of cellular and humoral immunity, enhances the synthesis of specific antibodies.

Indications: immunodeficiencies with a predominant lesion of the T-cell immunity, including chronic purulent processes and inflammatory diseases, burn disease, trophic ulcers, suppression of immunity and hematopoiesis after radiation or chemotherapy in cancer patients.

Side effects: allergic reactions.

Interferons- a group of biologically active proteins or glycoproteins (cytokines) synthesized by the cell in the process of a protective reaction to foreign agents (viral infection, antigenic or mitogen exposure). They are divided into 2 types. The first type includes α-interferons and β-interferons, which have predominantly antiviral and antitumor effects. The second type includes γ-interferons (produced by T-lymphocytes and NK-cells), which carry out a predominantly immunomodulatory effect. The immunotropic effect of γ-interferons is due to the activation of macrophages and all types of cytotoxicity, increased expression of antigens, regulation of sensitivity to cytokines. Along with activation of cellular and autoimmunity (synergism with tumor necrosis factor, IL2), inhibition of the humoral chain of the immune system is noted.

Indications for the use of γ-interferons is the prevention of opportunistic infections in AIDS, chronic granulomatosis, congenital T-cell immunodeficiencies; oncological diseases: tumors sensitive to interferon therapy (adenocarcinoma of the kidney, lung sarcoma, melanoma, neuroblastoma, tumors of the lymphoid endocrine organs, etc.), virus-induced tumors (papillomas of the larynx, bladder, basal cell skin cancer, etc.); autoimmune (rheumatoid arthritis, SLE), allergic diseases; treatment of severe bacterial infections. In clinical practice, recombinant interferon-γ preparations are used (produced by bacteria with an integrated interferon gene in their genome) - gamma feron, immunoferon. Pharmacology of preparations of other interferons is given in sec. "Antivirals".

Side effect dose-dependent fever with flu-like symptoms; asthenovegetative syndrome gastrointestinal disorders(anorexia, diarrhea) dermatological diseases; with prolonged use of high doses - reverse suppression of all elements of the bone marrow (thrombocytopenia, leukopenia, etc.).

Recombinant human interleukin 1-beta (betaleukin) is an analogue of natural IL-1. Able to bind to different types of cells, leads to a variety of biological effects (increase in body temperature, stimulation of the formation of prostaglandins, collagen synthesis by epidermal cells, bone resorption, cartilage degradation, etc.). One of the main properties of IL-1 is the ability to stimulate the functions of many types of leukocytes during the implementation of protective reactions. Stimulates both non-specific mechanisms of resistance, mainly associated with an increase in the functional activity of leukocyte neutrophils (increased migration, bactericidal and phagocytosis), and a specific immune response. It promotes the maturation and reproduction of T- and B-lymphocytes, and also participates together with antigens in the activation of T-lymphocytes, leads to the synthesis of IL-2 by these cells. Stimulates the proliferation of bone marrow stem cells, as well as the production of all types of colony-stimulating factor by various cells of body tissues. It has an antitumor effect, directly acting on some types of malignant cells or activating cytotoxic lymphocytes.

Indications: myelodepression caused by chemotherapy or radiotherapy; immunodeficiencies due to severe injuries on the background of chronic sepsis, post-traumatic osteomyelitis, after prolonged and extensive surgical interventions.

Recombinant human interleukin-2 ( proleukin) is a growth factor for lymphocytes. It is produced by a subpopulation of T-lymphocytes (Tx1) in response to antigenic stimulation and directly affects the proliferation of thymocytes, stimulates the growth and differentiation of T- and B-lymphocytes, potentiates the activity of macrophages, and increases the production of γ-interferon. IL-2 promotes the proliferation and activation of NK- and tumor-infiltrating cells.

Indications: sepsis of various etiologies, malignant neoplasms (cancer of the kidney, bladder, melanoma), tuberculosis, chronic hepatitis C.

Side effects of IL preparations: chills, hyperthermia, hemodynamic changes, allergic reactions.

Contraindications: autoimmune diseases, cardiovascular diseases, septic shock, high fever, pregnancy.

lykopis(glucosaminylmuramyl dipeptide) is synthetic analogue universal fragment cell wall almost all bacteria. Stimulates natural resistance, increases the bactericidal and cytotoxic activity of phagocytes, cytotoxic T-lymphocytes and NK cells, stimulates the synthesis of specific antibodies, IL, tumor necrosis factor, interferons and colony-stimulating factor, inhibits the biosynthesis of pro-inflammatory cytokines. In addition to the immunocorrective effect, it has anti-infectant and anti-inflammatory effects, which makes it possible to increase the effectiveness of antibacterial, antifungal and antiviral therapy. Assign in combination with antibiotics.

Indications: complex treatment secondary immunodeficiencies associated with chronic recurrent viral and bacterial processes (herpes, chronic infections upper and lower respiratory tract, pulmonary tuberculosis, pyoinflammatory processes, psoriasis, trophic ulcers, etc.). Undesirable action is not revealed.

Ribomunil- Ribosomal immunomodulator, which includes ribosomes of the main pathogens of respiratory infections (K. pneumoniae, Str. Pneumoniae, Str. Piogenes, H. influenzae), which induce the production of specific antibodies to the specified pathogens by the immune system. Ribosomes are 1000 times stronger immunogens than targets of microbial cells and contain the full range of antigenic structures characteristic of them. For adjuvant enhancement of the immunogenicity of ribosomes, as well as stimulation of nonspecific cellular and humoral immunity, cell wall proteoglycans were added to the preparation. K. pneumoniae. This gives a dual effect - a quick but short non-specific effect against various pathogens and a long-term specific protective effect against the main pathogens of respiratory infections. Stimulates the immune system due to the activation of macrophages, the synthesis of IL-1, IL-6, interferons, followed by stimulation of T, B-lymphocytes, NK cells, the production of specific secretory IgA.

Indications: chronic bronchitis, tonsillitis, pharyngitis, laryngitis, rhinitis, sinusitis, otitis.

Contraindications: acute stage of upper respiratory tract infection, autoimmune diseases, HIV infection.

For these indications, preparations of bacterial lysates are also used. broncho munal, Imudon.

BCG vaccine(BCG - from Bacillus Calmette - Goeren) contains non-pathogenic mycobacterium tuberculosis of cattle (produces tuberculin). Used for vaccination against tuberculosis. Assign in complex therapy for some malignant tumors. The BCG vaccine stimulates macrophages and, to a certain extent, T-lymphocytes. A positive effect is noted in cases of acute myeloid leukemia, in some variants of lymphoma (with the exception of Hodgkin's lymphoma), bowel cancer, and breast cancer.

Methyluracil belongs to the group of non-steroidal anabolic agents, while having a pronounced immunostimulating effect. It accelerates the processes of tissue regeneration (wound healing), increases the level of humoral (phagocytosis, antitilosynthesis, synthesis of lysozyme) and cellular immunity. Promotes the induction of endogenous interferon.

Indications: combination with antibiotics that suppress leukopoiesis, a long course of the infectious process, ulcerative colitis.

Side effect irritation of the mucous membranes of the digestive tract, which is accompanied by dyspeptic symptoms.

A number of synthetic immunostimulants are interferonogenams, that is, inducers of endogenous interferon ( prodigiosan, amixin, cycloferon, neovir, etc.) .

Herbal preparations(drugs echinacea (immunal), eleutherococcus, ginseng, rhodiola rosea etc.) are widely used in clinical practice as adaptogens and "soft" immunostimulants. They are used for immunorehabilitation and nonspecific immunocorrection. These are the only drugs with an immunostimulating effect that can be prescribed for immune dysfunctions, even without a preliminary assessment of the body's immune status and identification of exact violations in the immune system. Their mechanisms of action are not fully understood. It is known that under their influence, the activation of the energy and plastic support of the body's defense reactions occurs by accelerating the reactions of key enzyme systems and biosynthetic processes with the formation of a state of nonspecifically increased resistance of the body. They are able to simulate the activity of T- and B-lymphocytes, NK-cells, stimulate the production of endogenous interferon, IL-1 and other cytokines, enhance the phagocytic activity of granulocytes and macrophages, and the synthesis of antibodies. Almost all adaptogens have an anti-stress effect on the human body, and this, in turn, normalizes the course of immune reactions.

Basic principles of the use of immunotropic drugs. For a reasonable and purposeful use of immunotropic drugs, the doctor must first of all use all the possibilities to increase their effectiveness and reduce undesirable consequences. To do this, the following basic principles should be followed:

1. Immunotropic drugs are prescribed in combination with etiotropic and pathogenetic pharmacotherapy.

2. With absolute confidence in the advisability of prescribing immunotherapy, it is necessary to assess the nature and severity of immune disorders.

3. An important condition for the effectiveness of immunocorrection right choice a drug or a combination of several drugs, taking into account the direction of their action (activation, suppression, modulation), the degree of its selectivity in vitro to the immunocytes of a particular patient and mechanisms (the "pendulum" effect).

4. To achieve pharmacological effect immunocorrection, it is necessary to determine the optimal dose of the drug, the frequency of administration, the route of administration, the time of initiation of treatment, the duration of the course, taking into account a number of factors (age of the patient, gender, neuroendocrine, genetic characteristics, biological rhythms, accompanying diseases, etc.).

5. Simultaneous administration of several immunotropic agents is possible provided that they act on various parts of the immune system.

6. When prescribing immunotropic drugs, one should take into account their side effects, as well as the possibility of changing the spectrum of action of immunomodulators in a particular patient.

7. Be sure to take into account the immunotropic effect and side effects of accompanying therapy drugs.

8. It should be taken into account that the profile of the action of immunomodulators is preserved when various diseases, but subject to the same type of immunological disorders.

9. Expression clinical effect from the use of immunomodulators increases in patients who are in acute period diseases and in serious condition, as well as with repeated administration of the drug.

10. It must be taken into account that the elimination of the deficiency of one link of immunity compensates for the stimulation of another.

11. If it is impossible to conduct a thorough immunological examination, as an exception, the appropriate immunotropic agents can be prescribed on the basis of clinical manifestations indicating the presence of a defect in the corresponding link of the immune system.

12. You can not make hasty conclusions about the effectiveness of a particular tool. To eliminate immunological disorders, it takes from 30 days to six months or more, depending on the properties of the drug and the characteristics of the course of the disease.

13. For a complete recovery, a decrease in the frequency of relapses and chronicity of the disease, it is necessary to conduct a repeated immunological examination of patients in a timely manner, and, if necessary, treatment.

14. The effectiveness of the use of immunotropic agents increases in the case of simultaneous administration of vitamins, microelements, adaptogens and other biogenic stimulants. An important addition is the reduction of endogenous intoxication with the help of sorption therapy.

• In imidazole derivatives, levamisole (decaris) belongs, which has immunostimulatory and antihelminthic activity. Due to the inhibition of hematopoiesis (neutropenia, agranulocytosis) is limited in clinical application as an immunomodulator; used only for the treatment of helminthiasis.

Antitumor immunity is the main type of hereditary immunity that ensures the survival of multicellular animals, in the body of which, as calculations of somatic mutations show, about 1 million mutant cells arise in one day, a significant part of which undergoes tumor transformation. By quickly recognizing and destroying them, the immune system performs the function of homeostasis, which determines the normal development of organisms in the prenatal and postnatal periods.

The etiological basis of the occurrence of tumors. According to the now accepted views, cancerous degeneration of cells in animals is most often caused by integration DNA- and RNA-containing viruses. It usually does not appear immediately, since the genome of the integration virus in the chromosome of the host cell is repressed. The transformation of a cell into a malignant one occurs after derepression and reading information from viral oncogenes. Provoking agents of oncogene derepression can be exogenous or endogenous factors of the most diverse nature (see "Oncogenic viruses").

Types and mechanisms of antitumor immunity. There are two systems of antitumor protection: 1) innate, universal antitumor reactivity of the body, independent of the specificity of cancer antigens; 2) specific, which is induced by the antigens of emerging tumors, focused on the focus (blastoma).

Natural antitumor immunity is mainly due to normal killers, which destroy malignant cells upon contact, and TNF. The phagocytic reaction does not appear to be of great importance in the natural antitumor defense. Macrophages do not engulf living tumor cells, but, like normal killers, they may have a mechanism of cytolysis.

Specific anti-blastoma immunity is provided mainly by CTLs, but their effectiveness is determined by the immunogenicity of membrane tumor-specific transplant antigens (see "Oncogenic viruses"), the protective and adaptive mechanisms of malignant cells and their suppressive effect on immune system owner.

Mechanisms of protection of tumor cells from immune factors. There are two mechanisms of protection of malignant cells from immune surveillance. One of them is associated with a deficiency of recognition molecules on tumor cells, and the other is associated with masking (escape) of their antigens.

In particular, tumor cells are difficult to recognize by CTLs because they weakly or do not express MHC class I molecules at all. In addition, tumor cells do not express CD80 and CD86 molecules that react with the CD28 co-receptor, without a signal from which, instead of activation and differentiation anergy develops in CB8 + -lymphocytes, and often they are simply destroyed by the mechanism of apoptosis.

If a tumor antigen induces antibody formation, then specific immunoglobulins, reacting with it, instead of damaging tumor cells, often protect them from the action of cytotoxic T-lymphocytes or even enhance malignant growth. This is explained by the fact that the antibody blockade of tumor antigens on the membranes hides the foreignness of cancer cells. What is not clear is why antitumor antibodies do not opsonize malignant cells, promoting their phagocytosis or killing by NK cells. It should be noted that the foreignness of tumor antigens is masked not only by antibodies, but also by mucopolysaccharides, which always accumulate during the transformation of normal cells into malignant ones.

Tumor cells can also avoid immune surveillance by internalizing (immersing) the immune complex of antibodies with membrane antigens into the cell without subsequent resynthesis of surface antigens. It is possible that in some cases the membrane antigens of tumor cells become soluble and, being released into the intercellular fluid, “intercept” antitumor antibodies and block T-killers “on distant approaches”. It is possible that during the development of antiblastoma immunity in tumor cells, a mutation of genes occurs, which leads to the loss of specificity of their antigens.

It is assumed that the protection of tumor cells is due to their production of cytokines that reduce the activity of CTL. Such a function can, for example, be performed by TFR a and p, as well as IL-10, which inhibits the synthesis of cytokines by Txl cells (including y-IFN).

There is an idea that in the tumor process
often develops immunotolerance to tumors
antigens, which was reproduced in the experiment by inoculation of cancer cells that do not cause tumor formation and do not induce immunity.

The development of tumors can also be explained by the activation of suppressor cells. In this case, the role of suppressors can be performed by macrophages, hypothetical veto cells, Th2 lymphocytes, which are antagonists of Txl cells, or tumor cells themselves, producing the same cytokines as Th2 cells.

Human immune status

The body's resistance is ensured by the balanced action of many constitutional and acquired humoral-cellular factors of the immune system. The quantitative contribution of each of them to total immunity fluctuates around its characteristic average indicator (norm), which is called immune status.

Studies of the mechanisms of the immune status have revealed that the ability to respond to pathogens is genetically encoded. According to the strength of the immune response, some individuals can be highly responsive to one of them and weakly responsive to another, and the entire population is conventionally divided into three types - strong, weak and moderate. The immunoreactivity genes are called Ir genes. Among them, some control the process of antigen processing by macrophages, others control the rate of proliferation and differentiation of T- and B-cells, and others control the overall level of antibody production and cytokine synthesis. All these genes are linked to the major histocompatibility complex locus, encoding MHC antigens on immunocytes and thereby controlling the processes of their cooperation.

Age features of the formation of the immune status. The body of a newborn and children of the first 6 months of life reacts to the introduction of the antigen with a weak phagocytic activity and a low level of antibody production (mainly IgM). A fully-fledged immune system begins to function from the second year of life, when the normal process of IgG formation is established. By the 4-6th year, their titers reach the values ​​inherent in adults. Only a deficit in the production of secretory IgAS persists, which makes children highly sensitive to respiratory and respiratory pathogens. intestinal infections. Fully balanced functioning of protective factors is established only at the age of 15-16 and, under favorable conditions, is maintained throughout life. In older people, a decrease in the level of immunity occurs as a result of a violation of the process of recognition of antigens and the production of immunoglobulins, which most often occurs against the background of secondary immunodeficiencies that develop with somatic and infectious diseases. Usually they are temporary, functional in nature, disappearing after recovery, but if individual parts of the immune system are damaged, then immunodeficiencies progress.

The state of the immune status is judged by a number of tests of nonspecific and acquired resistance: by the quantitative content of complement, lysozyme, interferons a and P in the blood serum of patients, the phagocytic activity of macrophages and, most importantly, by the percentage or absolute number of T-lymphocytes, B-lymphocytes. cells and the content of immunoglobulins, the normal level of which in the blood is 1000-2000 T-cells / μl, 100-300 B-cells / μl, 0.5-1.9 g IgM / l, 8-17 g IgG / l , 1.4-3.2 g IgA/l.

When immunological disorders are detected, correction is resorted to using biologically active drugs that modify the immune response, have a beneficial effect on immunocompetent cells or on the regulatory products they produce.

Principles of Immunotherapy

Immunotherapy - treatment with immunotropic natural and synthetic agents acting on the immune system or immunological phase pathological processes. Among immunotherapeutic agents, there are immunostimulants-immunocorrectors that activate (correct) immunological processes, and immunosuppressors that inhibit (suppress) inadequately strong immune responses. All of them are called immunomodulators. Among them, according to the therapeutic effect, two groups are distinguished - with a predominantly stimulating or corrective effect and immunosuppressants.

Immunomodulators of stimulating and corrective action. According to the source of origin (receipt), 5 subgroups of stimulants-correctors are distinguished:

1) human immunoglobulin preparations (see "Immune sera");

2) peptides from bovine thymus extract (tactivin, thymalin, timoptan, thymomulin) used in the treatment of diseases affecting the T-system of immunity and autoimmune processes;

3) cytokines, first of all: a) recombinant interferons a (reaferon), P (betaferon), y (gammaferon), used to treat hepatitis, acute respiratory viral infections, malignant neoplasms, purulent and septic processes, b) interleukins, in particular IL-2 (proleukin and roncoleukin), effective in melanoma, leukemia and lymphomas, c) recombinant colony-stimulating factors (molgrastim, lenograstim), which are used to normalize hematopoiesis;

4) preparations from pseudomonad lipopolysaccharides (pyrogenal and prodigiosan), bacterial proteoglycans (licopid), Klebsiella and streptococcus ribosomes (ribomunil), yeast RNA hydrolyzate (sodium nucleinate), activating neutrophils, macrophages, endothelial cells, inducing the formation of anti-inflammatory ny cytokines and expression of adhesins;

5) levamisole, diucifon, thymogen and other synthetic immunomodulators used in immunodeficiencies.

Immunosuppressants. Substances of two generations are used as immunosuppressants. The first of these includes azathioprine, synthesized on the basis of 6-mer-captopurine, and cyclophosphamide, which disrupt the process of DNA replication and indiscriminately damage all dividing cells that enter into an immune response, resulting in disruption of tissue renewal processes and hematopoiesis. Unfortunately, the first generation of immunosuppressants weakens the body's resistance to infectious diseases and often contributes to the development of tumors.

More perfect second-generation immunosuppressants. The best of them is cyclosporin A, isolated from a soil fungus. Tylopocladium infantum, substance FK506 and the antibiotic rapamycin, obtained from streptomyces. Differing in structure and some features of the mechanism of action, they do not destroy, but only block the activation of T-lymphocytes and the production of IL-2, as a result of which they do not cause side effects and are used as ideal drugs to suppress the rejection reaction in organ and tissue allotransplantation, as well as in treatment of various autoimmune diseases. Sparing immunosuppressants were glucocorticoids, in particular prednisolone and especially drugs such as dexamethasone and betamethasone with high activity, long-term action and a pronounced anti-inflammatory effect. These hormonal preparations are used in the treatment of collagenoses and allergic diseases.

In recent years, attempts have been made to use immunotoxins as highly specific immunosuppressants, which are hybrid molecules consisting of monoclonal antibodies or cytokines associated with toxins (in particular, ricin) that can penetrate target cells and cause their lysis.