Immunostimulating therapy in the prevention of chronic cystitis. immune therapy. Immunomodulatory therapy. Immunostimulatory therapy. Types of immunostimulating therapy. Use of immunomodulators Nucleic acid preparations and synthetic polynukes
Discipline: Medicine
Kind of work: coursework
Topic: Immunostimulating Therapy
Interest in immunostimulatory therapy, which has a long history, has increased dramatically in recent years and is associated with the problems of infectious pathology and oncology.
Specific treatment and prevention based on vaccination are effective for a limited number of infections. For infections such as intestinal and influenza, the effectiveness of vaccination
remains insufficient. A high percentage of mixed infections, the polyetiology of many make the creation of specific preparations for immunization against each of the possible pathogens
not real. The introduction of sera or immune lymphocytes is effective only in the early stages of the infectious process. In addition, the vaccines themselves in certain phases
Immunizations can suppress the body's resistance to infections. It is also known that due to the rapid increase in the number of pathogens with multiple resistance to
antimicrobial agents, with a high frequency of associated infections, a sharp increase in immunization, can suppress the body's resistance to L-forms of bacteria and significant
number of serious complications, effective antibiotic therapy is becoming increasingly difficult.
The course of the infectious process is complicated, and the difficulties of therapy are significantly aggravated when the immune system and nonspecific defense mechanisms are affected. These violations can
be genetically determined or arise secondarily under the influence of various factors. All this makes the problem of immunostimulating therapy urgent.
With the widespread introduction of asepsis, which prevents the entry of microorganisms into the surgical wound, scientifically based prevention of infections in surgery began.
Only eighty-six years have passed, and the theory of infection in surgery has come a long and difficult way. The discovery and widespread use of antibiotics provided reliable prevention
suppuration of surgical wounds.
Clinical immunology is a young branch of medical science, but already the first results of its application in prevention and treatment open up broad prospects. Limits of Possibilities
clinical immunology is still difficult to fully foresee, but even now we can say with confidence that in this new branch of science, doctors are gaining a powerful ally in prevention and
treatment of infections.
1. Mechanisms of immunological defense of the body
The beginning of the development of immunology dates back to the end of the 18th century and is associated with the name of E. Jenner, who for the first time applied, on the basis of only practical observations, subsequently substantiated
theoretical method of vaccination against smallpox.
The fact discovered by E. Jenner formed the basis for further experiments by L. Pasteur, which culminated in the formulation of the principle of prevention from infectious diseases - the principle of immunization
weakened or killed pathogens.
The development of immunology for a long time took place within the framework of microbiological science and concerned only the study of the body's immunity to infectious agents. On this path were
great strides have been made in uncovering the etiology of a number of infectious diseases. A practical achievement was the development of methods for the diagnosis, prevention and treatment of infectious
diseases mainly by creating various kinds of vaccines and sera. Numerous attempts to elucidate the mechanisms that determine the resistance of the body against the pathogen,
culminated in the creation of two theories of immunity - phagocytic, formulated in 1887
P. Erlich.
The beginning of the 20th century is the time of the emergence of another branch of immunological science - non-infectious immunology. As a starting point for the development of infectious immunology were
observations of E. Jenner, and for non-infectious - the discovery by J. Bordet and N. Chistovich of the fact of the production of antibodies in the body of an animal in response to the introduction of not only microorganisms, but
generally alien agents. Non-infectious immunology received its approval and development in the work created by I. I. Mechnikov in 1900. study of cytotoxins - antibodies against
certain tissues of the body, in the discovery of human erythrocyte antigens by K. year.
The results of the work of P. Medawar (1946) expanded the scope and drew close attention to non-infectious immunology, explaining that the basis of the process of rejection of foreign tissues
The body also has immunological mechanisms. And it was the further expansion of research in the field of transplantation immunity that attracted the discovery in 1953 of the phenomenon
immunological tolerance - non-response of the body to the introduced foreign tissue.
Thus, even a brief digression into the history of the development of immunology makes it possible to assess the role of this science in solving a number of medical and biological problems. infectious immunology
- the progenitor of general immunology - has now become only its branch.
It became obvious that the body very accurately distinguishes between “own” and “foreign”, and the basis of the reactions that occur in it in response to the introduction of foreign agents (regardless of their
nature), the same mechanisms lie. The study of a set of processes and mechanisms aimed at maintaining the constancy of the internal environment of the body from infections and other foreign
agents - immunity, is the basis of immunological science (V. D. Timakov, 1973).
The second half of the twentieth century was marked by the rapid development of immunology. It was during these years that the selection-clonal theory of immunity was created, the regularities
functioning of various parts of the lymphoid system as a single and integral system of immunity. One of the most important achievements of recent years has been the opening of two independent
effector mechanisms in the specific immune response. One of them is associated with the so-called B-lymphocytes, which carry out the humoral response (synthesis of immunoglobulins), the other - with
a system of T-lymphocytes (thymus-dependent cells), the result of which is a cellular response (accumulation of sensitized lymphocytes). It is especially important to get
evidence of the existence of the interaction of these two types of lymphocytes in the immune response.
The research results allow us to state that the immunological system is an important link in the complex mechanism of adaptation of the human body, and its action is primarily
aimed at maintaining antigenic homeostasis, the violation of which may be due to the penetration of foreign antigens into the body (infection, transplantation) or
spontaneous mutation.
complement system,
opsonins
Immunoglobulins
Lymphocytes
Skin barriers
Polynuclears
macrophages
Histiocytes
Nonspecific
chesky
Specific
chesky
Specific
chesky
Non-specific
chesky
humoral
immunity
Cellular
immunity
Immunologists
cal protection
Nezelof imagined a diagram of the mechanisms that carry out immunological protection as follows:
But, as studies of recent years have shown, the division of immunity into humoral and cellular is very conditional. Indeed, the effect of the antigen on the lymphocyte and the reticular cell
carried out with the help of micro- and macrophages that process immunological information. At the same time, the phagocytosis reaction usually involves gu...
There are preparations of animal, microbial, yeast and synthetic origin, which have a specific ability to stimulate immune processes and activate immunocompetent cells.
An increase in the overall resistance of the body can, to one degree or another, occur under the influence of a number of stimulants and tonics (Caffeine, Eleutherococcus, Ginseng, Rhodiola rosea, Pantocrine, honey, etc.), vitamins A and C, Methyluracil, Pentoxyl and biogenic stimulants (Aloe, FiBS, etc.).
Natural interferons are widely used to create non-specific protection against viral infections, and preparations obtained from the thymus gland (Timalin, Timimulin, T-activin, Timoptin, Vilozen), bone marrow (B-activin), and their analogues obtained artificially (Timogen, Levamisole, Sodium nucleinate, Methyluracil, Pentoxyl; Prodigiosan; Ribomunil)
The ability of these drugs to increase the resistance of the body and accelerate the processes of regeneration served as the basis for their widespread use in the complex therapy of sluggish processes in infectious and other diseases.
Detoxification therapy
Among the drugs of pathogenetic therapy, in the first place are drugs of the detoxification series, which correct hemodynamics and absorb poisons:
A. Parenteral sorbents (colloids): Polidez; Poliglukin; Reopoliklyukin; Gelatinol; Alvezin; Reoman; Refortan; Stabizol, etc.). When using parenteral drugs, their molecular weight must be taken into account. With a weight of 30 - 60 thousand drugs have a hemodynamic effect, with a weight of less than 30 thousand - detoxification
B. Oral sorbents; Activated carbon; Enterodes; Polyphepan; Imodium etc.
B. Crystalloids: Ringer's solution; Trisol; Trisomin; Oralite; Glucosolan; Citroglucosolan; Regidron: Glucose 5%, etc.
When taking colloids and crystalloids, it is necessary to observe a ratio of 1: 3 per day (1 part of colloids and 3 parts of crystalloids)
D. Glucocorticoids: Prednisolone; Dexamethasone; Hydrocortisone; Cortisone etc.
Rehydration therapy
In many infectious diseases, especially intestinal infections, there is a loss of a large amount of fluid and salts. Therefore, it is often necessary to correct the water-salt balance
All rehydration is carried out in two stages:
A. Primary rehydration
The calculation is carried out taking into account the dehydration of the body, which is found by the weight loss of the patient.
1. Mild degree of dehydration (weight loss up to 3%) - 40-60 milliliters per 1 kg of body weight are administered over 4-6 hours.
2. The average degree of dehydration (weight loss up to 6%) - 70-90 milliliters per kg of body weight are administered over 4-6 hours.
3. Severe degree of dehydration (weight loss up to 9%) - - 90-120 ml is injected. per 1 kg of weight for 4-6 hours.
4. Very severe dehydration (more than 9% weight loss) - inject more than 120 ml. within 4-6 hours.
In mild forms of dehydration, oral dehydration is usually limited to glucose-salt solutions (Rehydron; Glucosolan; Citroglucosolan, etc.).
In more severe forms of dehydration, rehydration therapy is carried out parenterally with crystalloids (Disol; Trisol; Trisomin; Quatrasol; R. Ringer, etc.).
B. Supportive rehydration.
Secondary maintenance rehydration is carried out further for the entire period of fluid and electrolyte loss during vomiting and diarrhea, with a 10% supplement.
Anti-inflammatory therapy
A. Non-steroidal anti-inflammatory drugs.
· Drugs with a pronounced anti-inflammatory and analgesic effect: In decreasing strength of action - Butadione; Indomethacin; Clinoril; Tolectin; Ketorolac; Diclofenac; Fenclofenac and Aklofenac; Brufen and others.
· Drugs with a pronounced antipyretic effect: Paracetamol; Brufen; Naprosin; Ketoprofen; Surgam.
B. Steroid anti-inflammatory drugs.
Natural glucocorticoids - Cortisone; Cortisone; Hydrocortisone:
Synthetic analogues of glucocorticoids - Prednisolone; Methylprednisolone; Triamcinolone; Dexamethasone; Betamethasone:
B. Antihistamines
1st generation - Dimedrol; Pipolfen; Suprastin; Diazolin; Tavegil; Fenkarol:
2nd generation - Claritin; Bronal; Hismanal; Semprex; Zyrtec; Livostin; Allergodil; Kestin:
In practical medicine, combined drugs (NSAIDs + antihistamines + vitamin C) are more often used. There may be other combinations - Panadein; Antigrippin; Antiangin; Clarinase; Efferalgan; Koldakt; Coldrex and others.
Decongestive therapy
In infectious diseases, decongestant therapy is not often used and is usually associated with edema - swelling of the brain (hypertension syndrome) with neurotoxicosis and infectious-toxic encephalopathy. Parenteral diuretics are more often used (Lasix, Furosemide, Mannitol, etc.), in combination with hypertonic solutions (40% glucose solution, 25-50% magnesium sulfate solution, 10% sodium chloride and calcium solutions).
GBOU VPO Tver State Medical Academy of the Ministry of Health and Social Development of Russia
Department of Microbiology, Virology with a Course of Immunology
R.V. Mayorov, E.V. Nusinov
immunotropic therapy.
faculties of dentistry
Edited by V.M. Chervenets - Dr. med. sciences, prof., head. Department of Microbiology, Virology with a course of immunology.
Reviewers:
VC. Makarov - Dr. med. sciences, prof., head. Department of Infectious Diseases, BSEI VPO Tver State Medical Academy of the Ministry of Health and Social Development of Russia;
A.F. Vinogradova - Dr. med. sciences, prof., head. Department of Pediatrics of the medical and dental faculties of the Belarusian State Educational Institution of Higher Professional Education of the Tver State Medical Academy of the Ministry of Health and Social Development of Russia.
The methodological manual was approved at the meeting of the Central Committee for Combating International Relations of the TSMA from
Protocol No. _____
Maiorov, R.V., Nusinov, E.V.
The recommendations set out the basic principles of immunocorrective therapy from a modern standpoint, give a classification of immunotropic drugs, and give examples of schemes for prescribing immunotropic drugs. Guidelines are intended for students of medical, dental and pediatric faculties, undergoing a cycle of clinical immunology with allergology, as well as all those who are interested in immunology.
Roman Vladimirovich Mayorov – Ph.D. honey. Sci., Associate Professor of the Department of Clinical Immunology and Allergology, Allergist-Immunologist.
Nusinov Evgeniy Vladimirovich – Ph.D. honey. Sci., Associate Professor, Head of the Immunology Course of the Department of Microbiology, Virology, Allergist-Immunologist.
UDC 615-37 BBK 52.54
Maiorov R.V., Nusinov E.V., 2012 Design, layout, Alqvist edition, 2012
Purpose: To study the main groups of immunotropic drugs and methods of immunocorrective effects on the human immune system.
Teaching theme elements
1. Definition of terms immunotherapy, immunoprophylaxis, immunostimulator, immunomodulator, immunosuppressant.
2. Basic principles of immunocorrective therapy.
3. Classification of immunocorrective preparations.
4. Immunocorrective drugs of different groups (indications and contraindications for use, main side effects).
After mastering the material, the student should know:
1. Definition of terms immunotherapy, immunostimulant, immunomodulator, immunosuppressant.
2. The main options for immunocorrective effects on the human body.
3. The main mechanisms of the impact of immunocorrective drugs on the human body.
4. Basic principles of immunotherapy.
5. Differences between immunomodulators, immunostimulants and immunosuppressants.
6. Classification of the main immunotropic drugs.
7. Properties and indications for the use of various classes of immunocorrective agents.
8. Basic principles of the use of immunocorrective drugs.
9. Possibilities of immunocorrection in various types of immunological pathology: immunodeficiencies, allergic and autoimmune diseases.
The student must be able to:
1. Understand the main groups of immunocorrective drugs.
2. Prescribe immunocorrective agents, taking into account the pathogenesis, phase and stage of the disease, and the mechanism of action of the immunocorrective drug.
3. Be able to justify the appointment of an immunocorrective drug.
Control questions of students' knowledge:
1. What is immunotherapy?
2. What are the main indications for immunotherapy?
3. What types of immunocorrective effects do you know?
4. What is an immunostimulator?
5. What principles of immunotherapy do you know?
6. What groups can immunotropic drugs be divided into?
7. Name the main classes of immunotropic drugs, indications for use, side effects and contraindications.
List of abbreviations
CD4 - T-lymphocytes helpers
CD8 - T-lymphocytes killers Ig - immunoglobulin
NK - natural killer cells
IVIG - preparations of intravenous immunoglobulins G-CSF - human granulocyte colony stimulating factor
GM-CSF - granulocyte-macrophage colony-stimulating factor IL - interleukin
IFN - interferons KIP - complex immunoglobulin preparation
CSF - colony stimulating factor TNF - tumor necrosis factor
Basic terms
Immunotherapy - a method for treating and/or preventing the development of a human disease with the help of medicinal and non-drug means aimed at strengthening, suppressing and replacing the functions of the immune system.
Immunostimulants- drugs that predominantly enhance the immune response, bringing the reduced rates to
norms that activate immune responses or their individual links, both damaged and undamaged.
Immunosuppressants are drugs that suppress the immune response.
substances) identified forms of treatment and prevention in clinical
immunology:
∙ Immunostimulation.
∙ Immunosuppression.
∙ replacement therapy.
∙ ASIT.
∙ Vaccination, immunization.
Modern immunotherapy has several ways of influence:
I. The use of immunomodulators.
II. Substitution therapy - the introduction into the body of immunity factors in the case of genetically or phenotypically due to their deficiency.
accuracy (introduction of immunoglobulins, cytokines, etc.).
III. The introduction of highly specific preparations of exogenous therapeutic antibodies.
IV. Antibacterial and antiviral therapy.
v. Immunization with a given antigen:
Vaccination;
- allergen-specific immunotherapy.
VI. Systemic adaptation - a set of measures aimed at adapting the body to environmental conditions (therapeutic physical culture, hardening, diet, vitamin therapy, etc.).
VII. Efferent methods of influence: hemosorption, plasma -, cytopheresis, etc.
VIII. Physical methods: laser, ultraviolet and infrared irradiation of lymphoid organs and blood.
IX. Immune and genetic engineering: transplantation of organs, tissues and cells of the immune system, bone marrow, stem, dendritic and embryonic cells, gene therapy.
X. Immunosuppressive therapy.
The main mechanisms of action of immunotropic drugs:
1. Stimulation of the differentiation of immunocompetent cells by influencing the system of hematopoiesis.
2. Interaction of immunotropic agents with receptors of immunocompetent cells.
3. Stimulation or inhibition of cytokine synthesis.
4. Formation of specific active and passive immunity.
5. replacement therapy.
6. Combined immunocorrective effect and direct effect on the antigen (antiviral effect).
Indications for immunotherapy:
1. Primary and acquired immunodeficiencies.
2. Allergic diseases.
3. Autoimmune diseases.
4. Oncological diseases.
5. Infectious diseases.
6. Conditions after allotransplantation.
7. Diseases accompanied by a violation of regeneration.
8. Others.
Basic principles of immunotherapy:
1. Immunotherapy is prescribed based on the identified disorders in the immune system (data of immunological and allergological anamnesis, clinical and laboratory results of the examination, taking into account concomitant somatic diseases).
2. The choice of the type of immunotherapy is carried out taking into account the nature of the microflora (bacterial, viral, fungal) and the characteristics of the patient's nosological forms, his age, stage of the process. So, for example, the selection of immunocorrection depends on what stage the patient has - acute, subacute, chronic course, etc.
3. In cases where only changes in individual laboratory parameters are detected, but there are no clinical signs of immune deficiency, the administration of immunomodulators should be refrained from.
4. Immunotherapy usually complements basic treatment. Relatively rarely, an immunocorrective drug is prescribed as monotherapy, as in primary immunodeficiency. For example, the appointment of a patient with a chronic infectious disease, the use of adequate immunocorrection together with etiotropic anti-infective drugs leads to a much better effect than the appointment of the same drugs separately.
5. Accounting, registration and analysis of possible and identified side effects of immunotherapy.
6. Evaluation of long-term results of treatment.
IN Currently, there is no single generally recognized classification of immunotropic drugs. Therefore, in this manual only one of the many options is given, and methods of pharmacological immunocorrection and vaccination will be mainly considered. Other methods of influencing the human immune system are covered in detail in the elective classes of the department and other training cycles of a medical university.
Pharmacological immunocorrection.
Classification of immunocorrective agents: I. Immunomodulators
1. Preparations of endogenous origin.
∙ Immunoregulatory peptides derived from the central organs of the immune system (thymus, bone marrow).
∙ Cytokines (interferons, colony stimulating factors, interleukins, monokines).
∙ Immunoglobulins (specific and nonspecific).
2. Exogenous drugs.
∙ Preparations of microbial origin based on viruses, bacteria, fungi
∙ Synthetic (analogues of endogenous immunomodulators, immunomodulators of targeted synthesis, well-known drugs with the properties of immunomodulators): licopid, immunofan, polyoxidonium, sodium nucleinate, etc.
∙ Others: interferonogens, adaptogens, multivitamin preparations, preparations containing zinc, selenium, etc. and other trace elements.
II. Immunosuppressants
∙ Antimetabolites
∙ Alkylating compounds
∙ Antibiotics
∙ Glucocorticoids
∙ Cyclosporins
∙ Antibodies and their constructs
N.B. Any immunotropic drug that selectively acts on the corresponding component of immunity (phagocytosis, cellular or humoral immunity) will affect other components of the immune system to one degree or another.
Given this situation, however, it is possible to single out the leading directions of the pharmacological action of the main immunomodulatory drugs belonging to various groups according to the presented classification.
Immunomodulatory drugs
Experience in the use of immunotropic agents in medicine spans several decades, and to date, the final views on generally accepted international recommendations for the use of most of them have not been formulated. In this regard, it is necessary to be guided by the basic principles of the use of immunotherapy.
1. Immunomodulators of thymic origin.
These drugs are divided by origin into 2 groups:
1. Preparations of natural origin(T-activin, thymalin, thystimulin).
2. Synthetic origin (thymogen, immunofan).
They are mainly used for severe, recurrent, torpid to treatment course of infectious (usually viral, such as herpesvirus, papillomavirus infections) and oncological diseases. Their main target in the body is T-lymphocytes and the cellular immune response. With initially low levels of the T-cell link of immunity, drugs of this series increase the amount
stvo T-cells and their functional activity. This results in normalization of the immunoregulatory index (CD4/CD8 ratio), an increase in the ability of T cells to give a proliferative response to T-mitogens, and an increase in the production of the corresponding cytokines. At the same time, the functional activity of innate immunity factors increases: neutrophils, monocytes/macrophages and NK cells.
2. Immunomodulators of bone marrow origin.
The main target of exposure are B-lymphocytes. These drugs in immunodeficiencies restore the parameters of T- and B-immunity by stimulating the synthesis of antibodies, the differentiation of bone marrow cells into mature B-lymphocytes. Their action is based on the biological effects of myelopeptides (MP) in the bone marrow. So MP-1 restores the balance of activity of T-helpers and T-suppressors, MP-2 has an antitumor effect, MP-3 stimulates the activity of the phagocytic link, MP-4 stimulates the process of differentiation of hematopoietic cells. Representatives of this group of drugs are mielopid and seramil.
3. Cytokines
∙ Interferons (IFN). These are biologically active proteins with predominantly antiviral, immunostimulatory, and antiproliferative effects (Table 1), although the spectrum of their biological activity has not been finally determined. According to the structure and biological properties, IFN is divided into IFN-α, IFN-β, IFN-γ.
In Russia, IFN preparations are used primarily for viral infections from acute and chronic viral hepatitis, herpetic lesions to SARS. Interferon therapy is actively used in the complex treatment of oncological diseases.
Table 1 Biological properties of interferons
Type of interface |
Mechanism of action |
Preparations |
Enhances phagocytic activity |
Roferon-A, realdi- |
|
macrophage activity, cytotoxicity |
ron, reaferon-EC, in- |
|
CD16+ and CD8+, antigen expression |
teral, altevir, vi- |
|
new cell membrane. Suppresses |
feron, etc. |
|
reproduction of the virus in the cell, bac- |
Prolongation drugs |
terium, chlamydia, protozoa, ric- |
roved |
actions: |
||
Qetsii. Reduces antibody production |
pegasis, pegintron. |
|||
nie, differentiation and proliferation |
||||
cell radio, DNA and protein synthesis, |
||||
HRT and angiogenesis, which is additional |
||||
but causes antiallergic |
||||
cal and antitumor properties |
||||
Similar to IFN-α, but |
betaferon, |
|||
pronounced immunomodulatory |
||||
ripple effect. |
||||
Used in the therapy of scattered |
||||
th sclerosis. |
||||
having a pronounced |
||||
immunoregulatory and antiproliferative |
||||
ferative action on all stages |
||||
groin immune response. |
||||
Viferon rectal suppositories 150 thousand units, 500 thousand units, 1 million units.
In children under the age of 7 years, Viferon is used, containing 150 thousand units of IFN in 1 suppository; in children over 7 years of age and in adults, Viferon is used, containing 500 thousand units of IFN in 1 suppository.
As part of the complex therapy of influenza and other acute respiratory viral diseases (including those complicated by a bacterial infection), Viferon is used in age-specific dosages of 2 suppositories / day. every 12 hours daily. The course of treatment is 5 days.
There is a group of preparations of interferon synthesis inducers amixin, cycloferon, neovir. This group, when administered, stimulates the formation of endogenous IFN, which does not have antigenicity and ensures its sufficiently long circulation and is devoid of many side effects of recombinant IFN.
∙ Interleukins.
IN In clinical practice, two recombinant drugs have found the most active use: betaleykin and roncoleukin.
Betaleukin is a dosage form of recombinant human IL-1β. The drug stimulates hematopoiesis, immunity and early post-radiation recovery. In addition, the drug accelerates the recovery
reduction of bone marrow hematopoiesis, especially granulopoiesis, after the damaging effect of cytostatics and ionizing radiation. The immunomodulatory effect of the drug is realized by increasing the functional activity of neutrophilic granulocytes, inducing the differentiation of precursors of immunocompetent cells, enhancing the proliferation of lymphocytes, activating the production of cytokines and increasing antibody production.
Roncoleukin is a recombinant human IL-2. The drug stimulates the proliferation of T-lymphocytes, activates cytotoxic killers, which leads to an increase in antiviral and antitumor protective reactions. Mediated activation of B-lymphocytes, monocytes and macrophages determine its antibacterial and antifungal activity.
Examples of schemes for the use of group drugs:
Roncoleukin is a solution for s / c or / in administration in ampoules of 250 and 500 mcg. The drug is administered s / c or / in drip 1 time / day. in doses up to 2 mg.
The course of treatment for septic conditions of various etiologies (with post-traumatic, surgical, obstetric-gynecological, burn, wound and other types of sepsis): spend 1-3 s / c or / in the introduction of 0.5-1 mg with intervals of 1-3 days .
∙ colony stimulating factors
Human granulocyte colony stimulating factor
(G-CSF) is a glycoprotein that regulates the formation of functionally active neutrophils and their release into the blood from the bone marrow. G-CSF significantly increases the number of neutrophils in the peripheral blood already in the first 24 hours after administration. Preparations based on G-CSF: filgra-
stim, lenograstim, neupogen, grastim, granostim, leukostim, granocyte.
Main indications for use:
1. Neutropenia, in patients receiving intensive myelosuppressive cytotoxic chemotherapy for malignant diseases, with myeloablative therapy followed by allogeneic or autologous bone marrow transplantation;
2. Mobilization of peripheral blood stem cells;
3. Severe congenital, intermittent or idiopathic neutropenia in children and adults with a history of severe or recurrent infections, in patients with an advanced stage of HIV infection
to reduce the risk of bacterial infections when other treatments cannot be used.
∙ other cytokines.
Registered pharmaceutical preparations of this group
there is no py in our country. Two new domestic recombinant drugs TNF-α (allorin) and TNF-β (befnorin) are expected to enter the market. Also, the combined drug Refont, based on TNF-α and thymosin, is undergoing clinical trials. The drug has a direct (tumor cell apoptosis) antitumor effect. In terms of the spectrum of cytotoxic and cytostatic effects on tumor cells, the drug corresponds to human TNF-α, but has a 10-100 times lower overall toxicity.
4. Immunostimulants of microbial origin.
The action of this group of drugs is directed mainly to phagocytic cells. As a result, the functional properties of phagocytes are enhanced: phagocytosis and intracellular killing of absorbed bacteria increase. In addition, there is an increase in the humoral and cellular immune response: the synthesis of IgA, IgG, IgM increases, the activity of NK cells increases, the production of cytokines INF-α, INF-γ, IL-2, TNF-α increases.
Natural origin drugs include bacterial lysates (bronchomunal, IRS-19, immudon, ribomunil). The drugs of this group are proteoglycan complexes that are identical to the surface antigens of bacteria, most often causing infections of the upper respiratory tract and respiratory tract.
The main indications for the appointment of bacterial lysates:
1. Prevention and treatment of recurrent infections ENT organs (otitis, rhinitis, sinusitis, pharyngitis, laryngitis, tonsillitis), respiratory tract in patients older than 6 months;
2. Prevention of recurrent infections in patients at risk (often and long-term illnesses, before starting autumn-winter season, especially in ecologically unfavorable regions, patients with chronic diseases of the upper respiratory tract, chronic bronchitis, bronchial asthma, incl. children over 6 months and the elderly).
3. Complex therapy of conditions accompanied by secondary immunodeficiencies, including chronic infections of the upper and lower respiratory tract; in acute and chronic purulent
inflammatory diseases of the skin and soft tissues (including purulent-septic postoperative complications); herpetic infection, human papillomavirus infection, chronic viral hepatitis B and C, psoriasis, pulmonary tuberculosis.
Examples of schemes for the use of group drugs:
Licopid tablets 1 and 10 mg for sublingual use. Adults For chronic upper and lower respiratory infections
ways Likopid appoint sublingually 1-2 mg 1 time / day for 10 days.
5. Synthetic exogenous immunomodulators
∙ Nucleic acids.
The main pharmacological action of nucleic acids is
the stimulation of leukopoiesis, the processes of regeneration and repair, the functional activity of almost all cells of the immune system. Drugs of this group stimulate the functional activity of neutrophils and monocytes/macrophages, increase anti-infective resistance to infection by pathogenic microorganisms, probably due to the activation of phagocytosis, increase the functional activity of T-helpers and T-killers, increase B-cell proliferation and antibody synthesis. Nucleic acid preparations have an antioxidant effect, which is manifested in their ability to remove free radicals from the body. Due to these properties, nucleic acid preparations can reduce the damaging effects of radiotherapy and chemotherapy on the body. An example of such drugs is sodium nucleinate.
∙ Herbal preparations.
IN Currently, herbal preparations are widely used to stimulate the immune system. Some of these drugs are registered in Russia as immunostimulants: immunal, echinacea, tonsilgon, etc. It is believed that drugs of this kind are more appropriate to refer to adaptogens such as ginseng root, eleutherococcus, pantocrine, etc. The drugs of this group, to one degree or another, have an immunostimulating effect, in the form of stimulation of phagocytosis, an increase in the synthesis of INF, but they cannot be attributed to drugs, having a selective effect on the human immune system and evidence-based medicine speaks very carefully about their use.
∙ Chemically pure immunomodulators.
A heterogeneous group of drugs, whose representatives have a multidirectional effect on the human immune system.
This section presents data on the pharmacological activity of the latest generation of immunomodulators: galavite, groprinosin, polyoxidonium.
For example: The low molecular weight immunomodulator galavit has an immunomodulatory and anti-inflammatory effect. Its main pharmacological effects are related to the impact on the functional activity of macrophages. Their functional state is normalized, cytokine production and antigen presentation are restored. Galavit also stimulates the functional activity of neutrophils, natural killers. The consequence of this is an increase in the body's nonspecific resistance to infections. Indications for use: Acute and chronic inflammatory diseases of the gastrointestinal tract, accompanied by intoxication and / or diarrhea (gastric ulcer and duodenal ulcer, etc.), diseases of the urogenital tract (genital herpes, chlamydia, etc.), purulent-septic processes in pre- and postoperative period, for the prevention of surgical complications, chronic and often recurrent furunculosis, chronic inflammatory diseases that have arisen against the background of secondary immunological deficiency, in oncological diseases.
Groprinosin (inosine pranobex) - immunostimulating drug with antiviral activity. The immunostimulatory effect is due to the effect on the function T-lymphocytes (activation of cytokine synthesis), increased phagocytic activity of macrophages. Antiviral effect is associated with impaired replication as DNA- and RNA-containing viruses with pronounced interferonogenic activity. Indications for use: viral infections, especially in combination with immunosuppressive conditions (herpesviruses, measles, chickenpox, influenza, parainfluenza, etc.).
Polyoxidonium - immunomodulator with a wide range of pharmacological effects on the body. This effect consists of immunomodulatory, antioxidant, detoxifying and membrane-protective effects. The immunomodulatory effect of polyoxidonium is in the ability to activate poppy
rophages, enhance the cooperative interaction between T- and B-lymphocytes, increase their functional activity, significantly enhance antibody genesis.
6. Immunoglobulins.
Immunoglobulin preparations for intravenous administration, the so-called intravenous immunoglobulins, are widely used. Their use is indicated either as a replacement therapy for primary and secondary immunodeficiencies, or for immunomodulatory treatment in autoimmune diseases (Table 2).
The mechanism of action of IVIG is associated with neutralization of the antigen and circulating antibodies, blockade of Fc receptors on macrophages and the classical pathway of complement activation, elimination of circulating immune complexes, and modulation of the formation of pro-inflammatory cytokines. In addition, data were obtained on a change in the balance of Th1/Th2 towards Th1 and suppression of the synthesis of allo- and autoantibodies according to the feedback principle. The main
The indications for their appointment are primary and secondary immunodeficiencies, immune thrombocytopenic purpura, severe infectious diseases, prevention of infections after organ transplants, Guillain-Barré syndrome, etc. For the purpose of passive specific immunotherapy, a specific immunoglobulin or its fraction - gamma globulin for intramuscular injection is traditionally used : antistaphylococcal, antistreptococcal, antidiphtheria,
against Pseudomonas aeruginosa and others.
For example: Human antistaphylococcal immunoglobulin
contains antitoxic Ig at a concentration of at least 20 IU / ml, which is 3-10 times higher than their normal content in blood serum. Indications for use: purulent-septic processes, diseases of the musculoskeletal system (osteomyelitis) and other organs and systems.
Table 2 Examples of the algorithm for selecting intravenous immunoglobulin preparations
Clinical application of immunomodulators.
Despite the common point of view about the need to supplement therapeutic measures with an impact on immunity, in clinical practice, immunostimulating drugs are included in the treatment program quite rarely.
The expediency of prescribing immunomodulatory therapy is determined by the following factors:
1. The presence of insufficient anti-infectious protection in patients (for example, recurrent infectious diseases).
2. Diseases with severe manifestations of endotoxicosis (surgical diseases with purulent-septic complications, pancreatitis, burn disease, oncopathology, etc.).
3. The need to eliminate the consequences of iatrogenic effects (immunosuppressive therapy, etc.).
4. The choice of an immunomodulatory drug is determined by the stage of the disease (remission or exacerbation of the inflammatory process). For example, in case of acute inflammatory processes, septic condition, such immunomodulators as polyoxidonium, galavit, replacement therapy with intravenous immunoglobulins are recommended. During the period of remission or with a sluggish course, treatment with licopid, ribomunil, bronchomunal is justified, i.e. immunomodulators of microbial origin
5. Immunomodulators are prescribed in complex therapy simultaneously with etiotropic treatment.
6. The choice of an immunomodulatory drug and the scheme of its use is determined individually for each patient, depending on the severity of the underlying disease, concomitant pathology, and the type of immunological defect detected.
7. The main criteria for the appointment of immunomodulatory drugs are the clinical manifestations of immunodeficiency.
8. The presence of a decrease any indicator of immunity, revealed during an immunodiagnostic study in a practically healthy person, is not a mandatory basis for prescribing immunomodulatory therapy to him. Such people should be registered in an appropriate medical institution (observation group).
9. When carrying out immunorehabilitation measures, immunomodulators can be used as monotherapy, in particular in case of incomplete recovery after an acute infectious disease or in oncological practice.
10. When prescribing immunotropic therapy expediently
nie immunological monitoring.
Replacement therapy
Substitution therapy is a method of influence, in which exogenous substances are introduced into the body, which are lacking or absent in the body. These methods of treatment are rather aggressive methods of influencing the human body and are carried out mainly in two clinical situations:
1. A genetic defect in which a stable absence or a sharp decrease in the substance to be replaced is noted in the body;
2. Phenotypic damage to the body, accompanied by a pronounced defect in the immune system or other tissues of the body (massive burns, infections, etc.).
TO replacement therapy methods include, for example, transfusion of immunoglobulins used monthly for X-linked agammaglobulinemia, or other immunodeficiencies and conditions accompanied by a lack of antibodies; administration of a C1 inhibitor in congenital angioedema, red bone marrow transplantation, etc.
Example: The use of intraect in the treatment of X-linked agammaglobulinemia.
When carrying out these activities, it must be remembered that substitution therapy is carried out according to vital indications, and therefore it is necessary to obtain documented consent to the intervention, carefully explaining to the patient the possible complications and consequences of exposure.
In this case, there is often a risk of infection of the patient with viruses and prions from the medicinal product. Therefore, when carrying out replacement therapy, it is necessary to minimize this risk, for example, use immunoglobulins with a certificate of prion safety or interferons of recombinant origin that do not contain human blood albumins.
Highly specific exogenous antibodies for therapeutic purposes
This method of treatment is the introduction to a person of highly specific antibodies for therapeutic purposes. Distinguished by scientific novelty, it has a diverse range of clinical situations when it is in demand quite widely.
1. transplantology
Example: Orthoclon OKT3 is a monoclonal antibody that,
interacting with CD3, blocks the activity of T-lymphocytes. This drug has found its use in the prevention of acute kidney transplant rejection.
2. Autoimmune diseases
Remicade - blocks the activity of tumor necrosis factor. Applies
V treatment of Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis.
3. Infectious diseases
Palivizumab - interacting with the F glycoprotein of the respiratory syn-
cytium-forming virus neutralizes its activity and is used for prevention in children at risk.
4. Oncology
Rituxan - interacting with CD20 causes the induction of apoptosis, antibody- and complement-dependent cellular cytotoxicity. It is used in the treatment of non-Hodgkin's lymphomas.
5. Allergic diseases
Omalizumab - interacting with IgE, binds it, preventing degranulation of mast cells and basophils. Used in the treatment of atopic bronchial asthma.
Antibacterial and antiviral drugs
By introducing adequate doses of antiviral or antibacterial drugs, there is a decrease in both the number and the negative impact of infectious pathogens on the immune system and the body as a whole. This favorably affects the functioning of the immune system and improves the quality of medical care (for example: treatment of HIV infection).
System adaptation
The elements of a positive impact on the immune system and the body as a whole are maintaining a healthy lifestyle, hardening, good nutrition, an adequate regimen of physical activity, vitamin therapy, psychotherapy, etc. Adequate use of these methods allows you to maintain harmony between the inner world of a person and the environment.
Possible UIRS themes:
1. Contraindications for vaccination.
2. Principles of prescribing immunotropic drugs.
3. Immunocorrective therapy for recurrent herpetic infection.
4. Immunocorrection in chronic bronchitis.
5. Modern approaches to immunocorrection of frequently ill children.
6. Immune and genetic engineering as a way to influence the immune system.
7. Physical methods of immunocorrection.
8. Immunomodulators of thymic origin. Preparations, indications, contraindications, methods of preparation.
9. Monoclonal antibodies in clinical practice.
10. Immunomodulators of microbial origin. Preparations, indications, contraindications, methods of preparation.
11. Biological properties and pharmaceutical possibilities of using cytokines.
1. Allergology and immunology: national guidelines [Text] / ed. R.M. Khaitova, N.I. Ilyina. – M.: GEOTAR-Media, 2009. - 656 p.
2. Kovalchuk, L.V. Clinical immunology and allergology with the basics of general immunology [Text]: textbook / L.V. Kovalchuk, L.V. Gankovskaya R.Ya. Meshkov. – M.: GEOTAR-Media, 2011. - 768 p.
3. Khaitov, R.M. Immunology. Norm and pathology [Text]: textbook / Khaitov R.M., Ignatieva G.A., Sidorovich I.G. - 3rd ed., corrected. - - M .: OJSC "Publishing house" Medicine ", 2010. - 752 p.
4. Yarilin, A.A. Immunology [Text]: textbook / A.A. Yarilin. – M.: GEOTAR-Media, 2011. - 752 p.
Immunocorrective therapy - These are therapeutic measures aimed at the regulation and normalization of immune responses. For this purpose, various kinds of immunotropic drugs and physical effects are used (UV irradiation of blood, laser therapy, hemosorption, plasmapheresis, lymphocytopheresis). The immunomodulatory effect during this type of therapy largely depends on the initial immune status of the patient, the treatment regimen, and in the case of the use of immunotropic drugs, also on the route of their administration and pharmacokinetics.
Immunostimulating therapy represents a type of activation of the immune system with the help of specialized means, as well as with the help of active or passive immunization. In practice, both specific and non-specific methods of immunostimulation are used with the same frequency. The method of immunostimulation is determined by the nature of the disease and the type of disorders in the immune system. The use of immunostimulating agents in medicine is considered appropriate in chronic idiopathic diseases, recurrent bacterial, fungal and viral infections of the respiratory tract, paranasal sinuses, digestive tract, excretory system, skin, soft tissues, in the treatment of surgical pyoinflammatory diseases, purulent wounds, burns, frostbite, postoperative purulent-septic complications.
Immunosuppressive therapy - the type of influences aimed at suppressing immune responses. Currently, immunosuppression is achieved with the help of non-specific medical and physical means. It is used in the treatment of autoimmune and lymphoproliferative diseases, as well as in organ and tissue transplantation.
Replacement immunotherapy - This is a therapy with biological products to replace defects in any part of the immune system. For this purpose, immunoglobulin preparations, immune sera, leukocyte suspension, hematopoietic tissue are used. An example of substitution immunotherapy is the intravenous administration of immunoglobulins for hereditary and acquired hypo- and agammaglobulinemia. Immune sera (anti-staphylococcal, etc.) are used in the treatment of sluggish infections and purulent-septic complications. A suspension of leukocytes is used for Chediak-Higashi syndrome (a congenital defect of phagocytosis), hematopoietic tissue transfusion - for hypoplastic and aplastic conditions of the bone marrow, accompanied by immunodeficiency states.
Adoptive immunotherapy - activation of the body's immune reactivity by transferring non-specifically or specifically activated immunocompetent cells or cells from immunized donors. Nonspecific activation of immune cells is achieved by culturing them in the presence of mitogens and interleukins (in particular, IL-2), specific - in the presence of tissue antigens (tumor) or microbial antigens. This type of therapy is used to increase antitumor and anti-infective immunity.
Immunoadaptation - a set of measures to optimize the body's immune responses when changing geoclimatic, environmental, light conditions for human habitation. Immunoadaptation is addressed to persons who are usually classified as practically healthy, but whose life and work are associated with constant psycho-emotional stress and tension of compensatory-adaptive mechanisms. Residents of the North, Siberia, the Far East, high mountains need immunoadaptation in the first months of living in a new region and upon returning to their permanent place of residence, people working underground and at night, on a rotational basis (including duty personnel of hospitals and stations ambulance), residents and workers of ecologically unfavorable regions.
Immunorehabilitation - a system of therapeutic and hygienic measures aimed at restoring the immune system. It is indicated for persons who have undergone serious illnesses and complex surgical interventions, as well as for persons after acute and chronic stressful effects, large prolonged physical exertion (athletes, sailors after long trips, pilots, etc.).
Indications for the appointment of a particular type of immunotherapy is the nature of the disease, insufficient or pathological functioning of the immune system. Immunotherapy is indicated for all patients with immunodeficiency conditions, as well as for patients whose development of diseases includes autoimmune and allergic reactions.
The choice of means and methods of immunotherapy, schemes for its implementation should be based primarily on the analysis of the work of the immune system, with a mandatory analysis of the functioning of the T-, B- and macrophage link, the degree of involvement of immune reactions in the pathological process, and also taking into account the effect of immunotropic agents on a specific link or stage
development of the immune response, properties and activity of individual
populations of immunocompetent cells. When prescribing an immunotropic drug, the doctor in each case determines its dose, amount and frequency of administration.
Immunotherapy should be carried out against the background of good nutrition, taking vitamin preparations, which include micro and macro elements. An important point in the conduct of immunotherapy is the laboratory control over its implementation. Staged immunograms make it possible to determine the effectiveness of the therapy, to make timely corrections to the chosen treatment regimen, and to avoid unwanted complications and negative reactions. It should be emphasized that the unreasonable use of immunotherapy methods, the wrong choice of the means of its implementation, the dose of the drug and the course of treatment can lead to the prolongation of the disease and its chronicity.
Interest in immunostimulatory therapy, which has a long history, has increased dramatically in recent years and is associated with the problems of infectious pathology and oncology. Specific treatment and prevention based on vaccination are effective for a limited number of infections.
With infections such as intestinal and influenza, the effectiveness of vaccination remains insufficient. The high percentage of mixed infections, the polyetiology of many make the creation of specific preparations for immunization against each of the possible pathogens unrealistic. The introduction of sera or immune lymphocytes is effective only in the early stages of the infectious process. In addition, the vaccines themselves in certain phases of immunization are able to suppress the body's resistance to infections. It is also known that due to the rapid increase in the number of pathogens with multiple resistance to antimicrobial agents, the high frequency of associated infections, the sharp increase in immunization can suppress the body's resistance to L-forms of bacteria and the significant number of serious complications, effective antibiotic therapy is becoming increasingly difficult. The course of the infectious process is complicated, and the difficulties of therapy are significantly aggravated when the immune system and nonspecific defense mechanisms are affected. These disorders can be genetically determined or occur secondarily under the influence of various factors. All this makes the problem of immunostimulating therapy urgent. With the widespread introduction of asepsis, which prevents the entry of microorganisms into the surgical wound, scientifically based prevention of infections in surgery began. Only eighty-six years have passed, and the theory of infection in surgery has come a long and difficult way. The discovery and widespread use of antibiotics provided reliable prevention of suppuration of surgical wounds. Clinical immunology is a young branch of medical science, but already the first results of its application in prevention and treatment open up broad prospects. The limits of clinical immunology are still difficult to fully foresee, but now we can say with confidence that in this new branch of science, physicians are gaining a powerful ally in the prevention and treatment of infections.
More on Immunostimulating Therapy:
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