In addition to somatic and infectious diseases, widespread among people on the human body have an adverse impact on the health of social (and irrational lack of food, housing conditions, occupational hazard), environmental factors, health interventions (operational intervention, stress, etc.), in which primarily the immune system suffers, there are secondary immunodeficiency. Despite the continuous improvement of methods and tactics pursued by the basic treatment of diseases and use of drugs with a deep reserve of medication does not impact the effectiveness of treatment remains at a fairly low level. Often the cause of those characteristics in the development, course and outcome of disease in patients is the availability of any violations by the immune system. Studies in recent years in many countries around the world helped to develop and implement a broad clinical practice in the new integrated approaches to treatment and prevention of various forms nozologicheskih diseases using drugs immunotropnyh directional with the level and extent of violations in the immune system. An important aspect in preventing relapses and treatment of diseases, as well as in preventing immunodeficiency, is a combination therapy with a sound basic immunokorrektsiey. Currently, one of immunofarmakologii pressing tasks is to develop new drugs, combining the essential characteristics such as efficiency and security applications.
Immunity and immune system. Immunity - protecting the body from genetically alien agents endogenous and exogenous origin, aimed at preserving and maintaining the genetic homeostasis organism, its structural, functional, biochemical integrity and antigenic identity. Immunity is one of the most important characteristics for all living organisms created in the process of evolution. The principle of the protection mechanisms is to recognize, processing and elimination of alien structures. Protection by means of two systems - nonspecific (congenital, natural) and specific (acquired) immunity. These two systems represent two stages of the process of protecting a single organism. Nonspecific immunity serves as the first line of protection and as its final stage, and acquired immune system performs a specific function intermediate recognition and memorizing foreign agent and powerful means of connecting congenital immunity at the final stage of the process. Congenital immune system operates on the basis of inflammation and phagocytosis, as well as protective proteins (complement, interferon, fibronectin, etc.) This system responds only to corpuscular agents (micro-organisms, alien cells, etc.) and toxic substances, destroying cells and tissue, or rather , Corpuscular products at this destruction. The second and most complex system - acquired immunity - based on the specific functions of lymphocytes, blood cells, recognize alien macromolecule and reacting to them, either directly or evolving a protective protein molecules (antibody).
Immunomodulator - is drugs, restoring the application of therapeutic doses of immune system function (effective immune protection).
Immunomodulator (immunokorrektory) - a group of biological drugs (medications of the bodies of animals, vegetable), microbial or synthetic origin, has the ability to normalize the immune reactions.
There are currently allocated by descent 6 immunomodulator major groups:
* Immunomodulator microbial;
* Immunomodulator timicheskie;
* Immunomodulator kostnomozgovye;
* Cytokines;
* Nucleic acids;
* Chemically pure.
Immunomodulator microbial origin can be divided into three generations. The first drug authorized for use in medical as immunostimulators, was BCG vaccine, which has expressed the ability to reinforce factors as congenital or acquired immunity.
By the first generation of microbial drugs include such drugs as pirogenal and prodigiozan representing polysaccharides bacterial origin. Currently, because of pirogennosti and other side effects they are rarely applied.
By the second generation of microbial drugs are lizaty (Bronhomunal, I PC-19, Imudon, relatively recently appeared on the Russian pharmaceutical market Swiss drug production BRONCHO-Vaksom) and ribosomy (Ribomunil) bacteria, related mainly to the number of pathogens respiratory infections Klebsiella pneumoniae, Streptococcus pneumoniae , Streptococcus pyogenes, Haemophilus influezae etc. These preparations have dual use specific (vaktsiniruyuschee) and nonspecific (immunostimuliruyuschee).
Likopid, which can be attributed to the third generation of microbial drugs, is composed of natural disaccharides - glyukozaminilmuramila and acceding to the synthetic dipeptide - L-Alans-D-izoglutamina.
Timicheskih patriarch of the first generation of drugs in Russia has become Taktivin, a set of peptides, extracted from the thymus of cattle. By preparations containing complex timicheskih peptides are also Timalin, Timoptin and others, and by containing extracts thymus - Timostimulin and Vilozen.
Clinical effectiveness timicheskih first-generation drugs does not raise doubts, but they have one drawback - they represent an undivided mixture of biologically active peptides, quite difficult to standardize.
Progress in the field of medicines timicheskogo descent went through the creation of drugs II and III generations - synthetic analogs of natural hormones thymus or fragments of these hormones, possessing biological activity. The latter proved most productive. On the basis of one of the fragments, including amino acid residues timopoetina active center, was created synthetic geksapeptid Immunofan.
Kostnomozgovogo origin of the pioneers of drugs is Mielopid, which includes a set bioregulyatornyh peptide mediators - mielopeptidov (MP). It was found that various MP affect different parts of the immune system: some functional activity increases the T-helpers, while others suppress proliferation of malignant cells and significantly reduce the ability of tumor cells produce toxic substances; third fagotsitarnuyu stimulate activity of leukocytes.
Develop immune response regulation is implemented cytokines - immunoregulyatornyh complex set of endogenous molecules, which remain the basis for a large group of both natural and recombinant immunomodulatory drugs. The first group includes Leykinferon and Superlimf, for the second - Beta-leykin, Ronkoleykin and Leykomaks (molgramostim).
Group chemically pure immunomodulator can be divided into two groups: high-and low. The first concerns a number of known drugs, with an additional immunotropnoy activity. Their patriarch was levamizol (Dekaris) - fenilimidotiazol known protivoglistnoe vehicle, which has subsequently been identified expressed immunostimuliruyuschie properties. Another promising medicines from low subgroups immunomodulator is Galavit - derivative ftalgidrazida. The peculiarity of this drug is available not only immunomodulatory, but also expressed anti properties. By subgroup low immunomodulator also include three synthetic oligopeptides: Gepon, Glutoksim and Alloferon.
By high, chemically pure immunomodulator derived from chemical synthesis aimed include drug Polioksidony. It is a derivative N-oksidirovannoe poliegilenpiperazina with molecular weight of about 100 kD. The drug has a wide spectrum of pharmacological effects on the body: immunomodulatory, detoksitsiruyuschim, antioxidant and membranoprotektornym.
By medicines, characterized by pronounced immunomodulatory properties include interferon and interferon inducers. Interferon as an integral part of the cytokine network organism immunoregulyatornymi molecules are providing action on all the cells the immune system.
Pharmacological Effects immunomodulator.
Immunomodulator microbial origin.
In a prime target for the organism immunomodulator microbial origin are fagotsitarnye cells. Under the influence of these products increasing functional properties phagocytes (increased phagocytosis and killing sequestered intracellular bacteria), increased production of cytokines provospalitelnyh needed to initiate humoral and cellular immunity. As a result it may increase production of antibodies, education antigenspetsificheskih activated T-helper and T-killers.
Immunomodulator timicheskogo origin.
Naturally, under the name of a prime target for immunomodulator timicheskogo origin are T-lymphocytes. When initially lower rates of several drugs that increase the number of T-cells and their functional activity. Pharmacological Effects of synthetic dipeptide timusnogo Timogena is to increase the level of cyclic nucleotides, similar to the effect timusnogo timopoetina hormone, leading to stimulation of differentiation and proliferation predecessors T-cells in mature lymphocytes.
Immunomodulator kostnomozgovogo origin.
By immunomodulator received their bone marrow mammals (pigs or calves), applies Mielopid. The composition mielopida consists of six specific bone marrow mediators immune response, called mielopeptidami (MP). These substances have the potential to stimulate various parts of immune response, especially humoral immunity. Each mielopeptid has some biological effect, the combination of which makes its clinical effect. MT-1 activity restores normal balance of T-helper and T-supressorov. MT-2 suppresses proliferation of malignant cells and substantially reduces the ability of tumor cells produce toxic substances, the vast functional activity of T-lymphocytes. MP-3 stimulates activity fagotsitarnogo level of immunity and thus increases the antiinfektsionny immunity. MP-4 has an impact on the differentiation of hematopoietic cells, contributing to their more rapid maturity, ie has leykopoeticheskim effect. . When immunodefitsitnyh states drug restores indicators B-and T-Systems immunity, stimulates production of antibodies and functional activity immunocompetent cells, contributes to the restoration of a number of other indicators point humoral immunity.
Cytokines.
Cytokines - low gormonopodobnye biomlekuly produced activate immunocompetent cells and regulators are intercellular interactions. Their several groups - interleukin, growth factors (epidermal, nerve growth factor), colony factors hemotaksicheskie factors, tumor necrosis factor. Interleukin are the main participants in the development of immune response to the introduction of micro-organisms, the formation of inflammatory reactions, the implementation of antitumor immunity, etc.
Chemically pure immunomodulator
The mechanisms of these drugs is best seen by the example Polioksidoniya. This high immunomodulator characterized by a broad spectrum of pharmacological action on the body, including immunomodulatory, antioxidant, and detoksiruyuschy membranoprotektorny effects.
Interferon and interferon inducers.
Interferon - protective protein substances of nature, which developed cells in response to the infiltration of viruses as well as the effect of a number of other natural or synthetic compounds (interferon inducers). Interferon are nonspecific factors protect the body from viruses, bacteria, chlamydia, pathogenic fungi, tumor cells, but at the same time, they can act as regulators and intercellular interactions immune system. From this position as they relate to the immunomodulator endogenous origin.
Emphasis three types of human interferon: a-interferon (leukocyte), b-interferon (fibroblastny) and g-interferon (immune). g-Interferon has less antiviral activity, but also serves a more important role immunoregulyatornuyu. The schematic mechanism of action of interferon can be presented as follows: interferon in the cell linked to the specific receptor, which leads to the synthesis of protein cage around thirty, who named above and provide the effects of interferon. In particular, regulators are synthesized peptides, which are impeding the penetration of the virus in a cell, the synthesis of new viruses in the cell, stimulate the activity of cytotoxic T-lymphocytes and macrophages.
In Russia, history of drug interferon starts since 1967, the year was first created and introduced into clinical practice for the prevention and treatment of influenza and ARI human leukocyte interferon. Russia currently produces some modern medicines alpha interferon, which technologies are divided into natural and recombinant.
Inductors are synthetic interferon immunomodulator. Inductors interferon constitute a heterogeneous family of highly-ended - and nizkomiolekulyarnyh synthetic and natural compounds, the combined capacity to trigger the body’s own education (endogenous) interferon. Inductors interferon have antivirus, immunomodulatory and other characteristic of interferon effects.
Poludan (poliadenilovoy complex and poliuridinovoy acids) - one of the first inducers of interferon used with 70 - ies. His interferonindutsiruyuschaya activity is low. Poludan used in the form of eye drops and injections under konyuktivu when gerpeticheskih Keratitis and keratakonyunktivitah, as well as applications with gerpeticheskih vulvovaginitah and kolpitah.
Amiksin - low inductor interferon is a class fluoreonov. Amiksin promotes education in the body of all types of interferon: a, b and g. The maximum level of interferon in the blood achieved approximately 24 hours after receiving Amiksina, upgraded from its original values in dozens of times. An important feature is a long Amiksina circulation (up to 8 weeks) therapeutic concentrations of interferon after receiving a course of medication. A large and prolonged formulating stimulation Amiksinom endogenous interferon, it provides a wide range of universally antiviral activity. Amiksin also stimulates the humoral immune response, increasing production IgM and IgG, restores the balance T-helpery/T-supressory. Amiksin used for the prevention of influenza and other ARI, the treatment of severe influenza, acute and chronic hepatitis B and C, recurrent genital herpes, tsitomegalovirusnoy infection hlamidioza, multiple sclerosis.
Neovir - low interferon inductor (karboksimetilakridona derivative). Neovir induces in the body captions high endogenous interferon, especially early interferon alpha. The drug has immunomodulatory, antiviral and anticancer activity. Neovir apply at viral hepatitis B and C as well as uretritah, tservitsitah, salpingitah hlamidiynoy etiology, viral encephalitis.
The clinical application of immunomodulator.
The most reasonable application is submitted immunomodulator with immunodeficiency, causing increased infectious disease. The main target of immunomodulatory drugs remain a secondary immune deficiency, manifested by frequent recurrent, difficult to treat inflammatory diseases, infectious-all locations and any etiology. At the core of every infectious chronic inflammatory process is based on changes in the immune system, which is one of the reasons for persistence of the process. The study parameters are not always immune system can detect these changes. Therefore, if there is a chronic infectious-inflammatory process immunomodulatory drugs can appoint even if immunodiagnosticheskoe study does not reveal significant deviations in the immune status.
Generally, when such processes depending on the type of causative agent doctor appoints antibiotics, antifungal, antiviral or other chemotherapy drugs. According to experts, in all cases where funds are used for anti phenomena secondary immunological deficiency designate and immunomodulatory drugs.
The main requirements for immunotropnym drugs are:
* Immunomodulatory properties;
* High efficiency;
* Natural origin;
* Security, safety;
* Absence of contraindications;
* Absence of adjusting;
* Absence of side effects;
* Absence of carcinogenic effects;
* Absence of induction immunopatologicheskie reactions;
* Not cause excessive sensitization and not its potentsirovat
from other medications;
* Metabolizirovatsya and easily removed from the organism;
* Not to interact with other drugs and
have high compatibility with them;
* Neparenteralnye ways introduction.
There are currently developed and approved the basic principles of immunotherapy:
* Compulsory definition immune status before the immunotherapy;
* Definition of the level and defeat the immune system;
* Control of dynamics in the immune status of immunotherapy;
* Application immunomodulator only with the characteristic clinical signs and changes in immune status.
Appointment immunomodulator for preventive purposes in order to maintain the immune status (oncology, prompt intervention, stress, environmental, occupational exposure, etc.).
