INTERFERON (Latin the inter-prefix between; death, destruction + ferre to bear, transfer) — the low-molecular protein with antiviral properties containing a nek-swarm amount of carbohydrates including a glycosamine. It is opened in 1957 by Ayzeks and Lindenmann (A. Isaacs, J. Lindenmanu) who found that the cells infected with an influenza virus begin to develop and secrete the special protein interfering reproduction of viruses in cells to the environment. Further it was established that along with viruses ability to cause education And. many microorganisms and some substances received in the synthetic way possess (see. Inductors of interferon ).
Main property I. consists in the antiviral action which is shown in suppression of reproduction of infectious and oncogenous viruses. Depending on a species of animals, in cells to-rogo it is produced And., features of the inductor I. variations of some of its constants are observed. Pier. weight And. the Isoelectric point — ranging from pH 3 to 9 fluctuates from 12 000 to 160 000, and.
Due to the variability physical. - chemical properties I. began to define as a heterogeneous class of proteins. However data are obtained that it is reflection of a condition of aggregation of monomeric forms of molecules of substance. In particular, in And. the person molecules about a pier were found. weighing 96 000, 24 000 and 12 000. Heavier And. in salt solutions of low ionic strength it can be dissociated to more lung. Monomers on antiviral activity do not concede to dimeasures and oligomers.
Characteristic property And. specific specificity of its action is. Antiviral action And. it is most of all shown in an organism or cellular cultures of that species of animals, in cells to-rogo it it is received. Even in cells of sibling species he acts much more weakly. So, mouse And. renders in cells of a rat and hamster approximately by 20 times weaker antiviral action, than in cells of a mouse. In cells of the person, monkeys, chicken I. mice it is deprived of activity almost completely. An exception of this rule is And. the person, active and in cells of a rabbit.
And. has rather low antigenic activity. Homologous And. has no antigenic properties at all. Its drugs are stable with the broad range of pH. Even at pH 12,5 I. completely does not collapse and keeps up to 10% of activity. At pH 1,0 67% of activity are inactivated. It should be noted that sharply acid pH values are pernicious for viruses while And. not less than 7 days show stability. Therefore acid resistance And. it is used for an inactivation of an infectious virus in drugs I.
Heat stability of drugs I. depends on its origin. And. is steadier than birds against action of heating, than And. mammals. It is long keeps And. activity at 4 — 10 °, and also in the frozen state. Being dried up by a lyophilic method, And. keeps activity for a long time. And. it is possible to clear and concentrate, using various methods applied in work with proteins. Cleaning is very effective And. by method of a chromatography on solid-phase immunoadsorbent.
Ability to synthesize And. in vitro possess as primary, diploid, and intertwined lines of cells of fibroblastichesky and epithelial types. Active producers And. also elements of white blood of the person and animals are.
Quantity formed in cellular cultures And. is defined by specific and shtammovy features of viruses and cells, activity of viruses in this culture of cells and plurality of an infection. It is known that the same virus can induce synthesis And. in one cellular system and not to show this ability in another.
And. it is formed also in an organism of the people and animals infected with viruses. Education And. goes usually in parallel with reproduction of a virus. However in certain cases maximum of products And. advances or lags behind a maximum of a reproduction of a virus in selectively struck fabrics a little. At the same time at some viral infections (experimental flu) And. the virus disappears from an organism earlier, than.
And., induced at animals by intravenous administration of a virus, early (in 1 — 2 hour) appears in blood and rather quickly disappears (in 24 — 36 hours it is not found in blood any more). And., early revealed in blood after intravenous administration of the inductor, call serumal And. Its education is not connected with reproduction of a virus. Elimination half-life And. from a bed of blood it is estimated several minutes.
And. is probably one of the most biologically active agents. E.g., chicken And. at the 20th 000-fold cleaning had specific activity 1,6 X 10 3 unit on 1 mg of protein, and mouse And. — 3 X 10 8 piece. But even these materials were not rather cleared.
And. has no selective antiviral activity and affects practically all viruses. Only on the infection caused by a virus fasten, it was not succeeded to influence And., its inductors. Intensity of action And. on various viruses it is not identical: one viruses more, and others are less pliable to I. Ustanovleno's action distinction in sensitivity not only between different types of viruses, but also between strains of one and that about a look. It is necessary to consider that results of definition of activity And. depend not only on sensitivity of a virus, but also on sensitivity of fabrics to I. Izvestno that some cellular cultures, being good producers And., are not sensitive to its action.
Some viruses induce special inhibitors in cells (stimulon, a bloker, the antagonist I., etc.) which suppress education or action And. It is necessary to emphasize that the described properties are inherent only in separate strains of viruses which cause formation of inhibitors I. only in certain oozes of cellular cultures.
Mechanism of action
And. directly does not inactivate viruses or their nucleinic to - you, does not interfere with adsorption and penetration of a virus into a cell, and also its deproteinization. And. shows the action at an intracellular stage of a reproduction of a virus.
Mechanism of interaction And. with cells in which it induces an anti-virus state, remains not clear. According to one authors, And. can induce an anti-virus state in cells without the found loss of activity, on others — protective action And. it is connected with intensity of its absorption. For manifestation of action And. integrity of cellular receptors and ability of cells to synthesis of RNA and proteins shall remain that, according to a number of researchers, testifies in favor of its mediated action by induction in cells of special antiviral protein (AVB).
Finally the issue of the molecular mechanism of antiviral action of I. Dopuskayetsya action is not resolved And. at the level broadcastings (see), and transcriptions (see). In favor of the first data on that testify, as., without influencing synthesis of virus-specific RNA, inhibits synthesis of virus proteins. And. not only reduces amount of the formed virus-specific polypeptides in the infected cells, but leads also to shortening of polypeptide chains. Assume, as. or AVB can modify virus RNA so that it loses ability to participate in education by the policy.
Supporters of action And. at the level of a transcription are based on the data on inhibitory action And. on a transcription of early virus RNA. This ingibition is connected with suppression of the virusindutsirovanny synthesis caused by a virionny RNA-dependent polymerase.
Some authors allow existence of two ways of action And. — on a transcription and broadcasting — with dominance of one of mechanisms at various viral infections. The most widespread is the assumption that as a result of influence And. broadcasting is broken, as causes impossibility of implementation of the subsequent stages in a reproduction of a virus (see. Viruses ).
Methods of indication and titration
by the Most sensitive method of titration And. the definition of its action on intensity of reproduction of a virus in cells revealed or on reduction of virus hemagglutinins, or on decrease in «harvest» of an infectious virus is considered.
For definition of activity And. apply the methods based on suppression more often And. a cytopathic effect of a virus in test tubes or suppression of plaques by it (a method of negative colonies of a virus across Dulbekko). And, the last is 16 — 32 times more sensitive than a method of titration on suppression of a cytopathic effect in probirochny cultures.
It must be kept in mind that the maximum resistance processed And. cells not less than 7 — 8 hours after introduction of drug develop. If. from cellular cultures time is removed washing after achievement of a maximum of resistance, a cell a nek-swarm keep immunity to a virus. However a long incubation of cells after removal And. leads to gradual loss of stability.
On sensitivity of system to And. many factors exert impact: a type of an indicator virus and its dose, type of cellular culture, age of cells, duration of an incubation of cells with And. and pH of the environment. For standardization of methods of titration And. it is recommended to enter well studied standard of activity into each experience And. and to define activity of the studied material in the international units.
As suppression of reproduction of viruses is the major function I., its quantity which is formed in an organism at a viral infection is important in manifestation of antiviral resistance. Than more it is developed And. in an organism, especially protected there is this individual. At the same time potentialitys of development And. at certain people and animals are not identical. Ability to education And. it is descended under Mendel's laws (see. Mendel laws ). Despite genetic determinancy of this sign, its phenotypical manifestation essentially changes at various stages fiziol. development of an organism. Ability of an interferonoobrazovaniye is rather low at babies, gradually increases at children 1 years are more senior, reaching a maximum at adults. After 60-year age development And. sharply decreases.
Ability to development And. changes also at various adverse effects on an organism: cooling, radiation, noise stress, drunkenness, etc. To decrease in education And. conducts also disbolism caused both by hyperfunction, and a hypocrinism.
To develop And. practically any cell of an organism can. Development And. begins immediately after penetration of a virus into an organism. It is produced by those cells which initially are surprised a virus, i.e. development And. begins already in entrance infection atriums. At the same time, even if the infection is limited to entrance gate, nevertheless a certain quantity of cells perishes. Those cells which the first came into contact with a virus collapse. Formed by these cells And. does not manage to provide resistance of cells producers, however surrounding cells for the account And. find resistance to a virus.
And. is considered as one of the most important factors of protection of an organism at primary viral infection. At the same time it is not always possible to find compliance between education And. and an outcome of a viral infection (see. virus-induced immunity ).
Anti-infectious action And. it is not limited only to viruses, and extends also to others intracellular parasites. In particular, And. suppresses intracellular reproduction of the causative agent of trachoma, a malarial plasmodium, toksoplazm and rickettsiae. U I. also anti-toxic activity is revealed. In the presence And. cellular cultures are steadier as in the relation ekzo-, and endotoxins.
And. influences activity of antiteloobrazuyushchy cells: small doses And. stimulate their activity, and high concentration — brake.
Believe, as. plays a role in cellular immunity. In particular, lymphocytes of the people and animals sensitive to tuberculine produce And. in response to influence of the purified protein of tuberculine. At individuals, insensitive to tuberculine, And. it is not produced. These data are supported also with the fact that the resistance of animals to viral infections connected with reaction of hypersensitivity of the slowed-down type also in a certain measure is caused
by I. I. strengthens phagocytosis and influences reaction of graft rejection, suppresses transformation of cells oncogenous viruses, growth of tumor cells of in vivo and in vitro, increases cytotoxicity of lymphocytes. Assume also, as. participates in control of differentiation of cells in an organism.
And. can change the answer of cells to virus or not virus inductors I., either strengthening, or reducing development And. Besides, under influence And. cells become their two-filamentous RNA, sensitive to destruction.
Drugs I. suppress growth of normal cells, oppressing synthesis of cellular DNA and proteins, owing to blockade of broadcast of cellular IRNK. Full confidence that And. causes anti-cellular activity of drugs I., is not available. Even the most high cleaning drugs I. during the check the electrophoretic method was heterogeneous.
Proceeding from the revealed variety of functions, consider that at the heart of various biol, phenomena caused And., its ability to regulate synthesis of macromolecules in a cell lies.
Use And. for prevention and treatment of viral infections perhaps in two main directions: 1) use of ready drug (exogenous And.), the person received in system of cells, 2) stimulation in own, so-called endogenous
I. I. organism renders the expressed preventive and to lay down. effect at the diseases caused by many viruses. Its use at viral infections with preferential focal lesion is reasonable (dermatitis, eye diseases, etc.). Especially important acknowledges the possibility of use And. at respiratory viral infections which etiology is various and therefore, their vaccinal prevention is extremely complicated.
The best effect gives And. at preventive use. At development of a disease its whenever possible early use is necessary. One of the main ways of increase in efficiency And. increase in frequency rate of its introduction is.
From other aspects of practical application And. it is necessary to mention the technique of definition of products developed by V. D. Solovyov and T. A. Bektemirov (1967) And. leukocytes of in vitro, edge it was called the interferon reaction of leukocytes (IRL). It is established that IRL at a number of viral infections can be used as an indicator of an immunoreactivity of an organism. At the same time it is shown that definition of products And. by leukocytes it can be used for assessment of reactivity of an organism normal and at patol, conditions not of a virus origin.
From additional materials
Distinguish leukocytic, fibro - blast and immune interferon. All of them represent to Indus-tsibelnye the proteins having ability to cause in cells a razfibroblastnokhma I. Interferon produced by leukocytes in response to influence of mitogens, e.g. lectins (see), at proliferation of lymphocytes or produced by sensibilized lymphocytes in response to specific bacterial or viral antigens is called interferon II of type or immune And. Distinctive properties of interferon of I and II types, in addition to conditions of their receiving, are also antigenic distinctions and their stability in the environment with pH 2,0 (interferon I of type is steady in this environment, and interferon II of type is unstable). Division of II. on two types (I and II) it is replaced with division with the types reflecting as a source of receiving And., and their main properties. According to such approach distinguish and - interferon (leukocytic interferon I of type), R-interferon (fibroblastny interferon I of type) and at - interferon (immune interferon II of type).
The international committee on the nomenclature of interferon it is offered to designate And. bukvakhm of the Latin alphabet of IFN, and types I. — letters of the Greek alphabet and, | 3, at. For designation of animals, from to-rykh cells — producers are received And., use of the corresponding prefixes is recommended. So, e.g., for designation human And. it is necessary to use a prefix (English human, armor. humanus human) — HuIFN, for designation of mouse interferon Mi's prefix (English mouse, armor. mus a mouse) — MuIFN, etc. At the description separate And. with various a pier. vesokhm (weight) after the name I. in brackets it is necessary to give this size in kilodaltona. When And., produced by cells, represents skhmes the known types I., it is recommended to use in the name the instruction on major component. So, And., produced by lymphoblastoid cells and consisting of mix leukocytic (87%) and fibroblastny (13%) interferon, it is recommended to designate HuIFN-a(Ly). At the same time the possibility of the instruction in brackets of a source of such interferon, napr is not excluded, leukocytic interferon of the person in that case hmozhno to designate HuIFN-a(Le), and lymphoblastoid — HuIFN-a(Ly). Interferona, received by means of methods of genetic engineering (see), received genetically engineered or clonal P.' name, bacterial And., genoferon.
Polypeptides and - and r-interferonov consist of 165 — 166 amino-acid remains, the Crimea 21 — 23 amino acids of the alarm polypeptide which is chipped off in the course of a post-transmitting prevra-
of a shcheniye of a molecule of interferon and its secretion from a cell precede. Structures and-and r-interferonov have a certain similarity (to 30% of a homology at the amino-acid level) whereas the sequences of amino acids in polypeptides and - and at-in-terfe r it<) in a harakta r and z a cosiness I am l and sh extremely insignificant coincidence. On average on one molecule I. less than one carbohydrate rest (mines glucose or a galactose of mines) are necessary. It contradicts earlier existing opinion, as. represents a glycoprotein. Molecules human leukocytic And. in the majority are deprived of carbohydrates.
Distinctions in amino-acid composition and the sequence of amino acids in polypeptides reflect distinctions in structure of the genes determining their synthesis. In particular, the gene family human and - interferon contains at least 20 various genes. Nek-rye from these genes is nonallelic, other allelic options. Much less genes (to five) code synthesis (3 interferon. The quantity of structural genes for at - interferon is unknown.
Structural genes And. the person are localized in the 9th chromosome, but the possibility that a part them is not excluded (or genes activators of synthesis And.) belongs to the 2nd, 5th and 13th chromosomes. In the course of induction And. there is an activation of the corresponding genes that leads to the subsequent synthesis (transcription) of template-RNA (MRNK), broadcasting a cut and causes formation of polypeptides I. Mechanism of education And. it is subdivided into two phases — induction and products of interferon. The I phase — induction (process is sensitive to inhibitors of synthesis of RNA) — consists of the following stages: adsorptions of the inductor I. on a surface of cells; interactions of the inductor I. with the corresponding cellular receptors; initiations of induction And.; derepressions of genes And.; transcriptions (see) template-RNA for interferon. The II phase — products (process is sensitive to inhibitors of synthesis of protein) — includes the following stages: broadcast of RNA with formation of polypeptide I.; post-trance-lyatsionnye of transformation of polypeptide I. with formation of a so-called inter-feroid (the predecessor I.); possible glycosylation (accession of aminosugars) interferoi - yes, formation of a molecule I.; release (secretion) And. from a cell.
And. in cells it is synthesized after induction of de novo. Hypotheses of existence in cells of the predecessor and his activation in the course of induction were wrong. Practically all yadrosoderzhashchy cells of vertebrata are capable to form And., however the cells not capable to products are known And., napr, the intertwined cells of the VER O line.
Process of education various And. has different duration. So, synthesis of wasps - or [3 interferon comes to the end within 8 — 12 hours, at at - interferon this process is longer. E.g., sensibilized lymphocytes of the person produce at - interferon in response to influence of a virus of a variolovaccine in 7 — 8 days.
Genetically engineered method of receiving And. schematically comes down to the fact that from the zooblasts producing And., allocate and clear MRNK for And. and on a matrix of MRNK by means of a revertaza (see) receive DNA copies — I. Zatem these genes use so-called complementary DNA (KDNK), or artificially synthesized gene for designing of recombinant plasmids (see), in to-rykh KDNK is connected to active prokaryotic promoter (see the Opera). The received himerny plasmids implement in a bacterium (Escherichia coli, Bacillus subtilis) or yeast, to-rye and begin to produce And., the artificial gene to-rogo was implemented in a microbic cell. In such way it is possible to receive clones of the bacteria or yeast producing And. a certain type in rather large numbers, and material inputs on receiving it And. it is many times less, than costs of production of the same quantity And. in suspensions of leukocytes or in cellular cultures. However such genetically engineered method of receiving And. and received And. are not deprived of a number of shortcomings. So, e.g., separate clones of microbes produce, as a rule, only those polypeptides I., the artificial gene to-rykh was entered into cells producers, and natural And. consists of population of the polypeptides coded by different genes. Besides, cleaning is necessary And., received by a genetically engineered method, from antigens bacterial (or barmy) origins, etc. Exit And., produced by bacteria, it is rather high — 8 * 107 — 2-108 PIECES in 1 l that testifies to prospects of this method.
And. not only development of resistance of cells to viral infections causes, but also influences various reactions of immunity. And. it is necessary to consider as the regulator (stimulation or oppression) of various mechanisms of an immune response. To the stimulating effects And. carry: increase in resistance of cells to virus infection, increase in activity of natural lymphocytes-kil-lerov (see Tumours), strengthening of phagocytosis, an expression of antigen of the main complex of histocompatability (see Incompatibility immunological), strengthening of products And, the cells processed homologous And. in small doses (priming effect). To ugnetayushchikhm to effects And. refer oppression of synthesis of antibodies, suppression of anaphylactic reactions (see the Anaphylaxis), suppression of hypersensitivity of the slowed-down type (see the Allergy), oppression of proliferation of lymphocytes, suppression of growth of cells (including and tumoral), suppression of reaction to a transplant and reactions a transplant against the owner, suppression of a complement, suppression of products And. the cells processed homologous And. in high doses (blo))))))))))))).
Efficiency of influence And. on reaction of immunity it is various and I. Tak depends by nature, the greatest anti-proliferative action immune interferon (possesses at - interferon), to-ry was more effective | 3-and and-interferonov.
And. has also ability to protect cells from ionizing radiation, antimito-gene activity is inherent in it, it can have anti-toxic effect. Long time the question of antibacterial activity of interferon since the native or partially purified drugs I was discussed. possessed antibacterial action. However the subsequent experiments made with well purified drugs I., showed that they are deprived of antibacterial activity.
High biol. efficiency And., its ability to influence reactions of immunity does not allow to explain its action on cells and the more so on an organism with any uniform simple mechanism. The mechanism of antiviral action is the most studied And. Necessary condition of successful development in cells of the anti-virus resistance caused And., preservation of cellular metabolism is (oppression of synthesis of cellular RNA and protein interfered and even completely prevented this effect And.).
Process of interaction And. with sensory cells it is possible to subdivide into a number of stages: adsorption And. on cellular receptors (a question of penetration And. in a cell it is not solved finally, there are many data on that, as. does not get into cells); induction of development of an anti-virus state; development of anti-virus resistance; emergence of the expressed resistance to virus infection.
Development of anti-virus resistance in cells is controlled by two genes. One of them is localized in a distal segment of a long shoulder of the 21st chromosome and determines synthesis of a superficial receptor for interferon (a locus of IFRC), and another, being in the 16th chromosome, regulates an anti-virus state.
Fig. Diagrammatic representation of the mechanism of anti-virus effect of interferon:
interferon, interacting with receptors of a cell membrane, induces synthesis of enzymes — I' - L '-izooligoadenilatsintetazy and protein kinases. After infection of a cell with a virus under the influence of the two-chained replicative form of virus RNA which is formed in a cell there is an activation of these enzymes. At the same time 2 '-5' ~ the izooligoadenilatsintetaza causes activation of endonuclease which, in turn, causes destruction of virus RNA; the protein kinase causes disturbance of synthesis of virus proteins, thus process of reproduction of a virus is broken.
Long time there were unresolved questions connected with the molecular mechanism of effect of interferon. In the late sixties 20 century the theory about formation of anti-virus protein dominated, the main action to-rogo came down to suppression of synthesis of virus proteins (oppression of process of their broadcasting). In the subsequent this theory underwent review. It turned out that after influence And. on cells in them the synthesis of cellular RNA and proteins leading to accumulation of three cellular proteins which are enzymes — protein kinases, 2 '-5 '-izooligoade-nilatsintetazy and endonucleases (fig.) is activated. The synthesized enzymes until infection of a cell with viruses remain inactive. They are activated only after infection, more precisely after education in a cell of a two-chained replicative form of virus RNA. Emergence of this RNA form also leads to activation of the called enzymes synthesized after influence And., but not active up to this point. Their complex action also causes anti-virus effect as synthesis of virus macromolecules is broken, as due to direct impact on processes of broadcasting (see), and time-r at hi e N iya in and r ny R N K.
Mekhanizm' mustache of action And. at other manifestations of its activity it is unknown. Even studying of the mechanism of anti-proliferative action And. is at the most initial stage. It is established, as. suppresses division of tumor cells, reduces in them intensity of synthesis of macromolecules, in particular DNA. Antineoplastic action And. in an organism, apparently, it is connected as well with activation of natural lim-fotsitov-killers.
Despite imperfection of our knowledge of the mechanism of action And., there is its intensive implementation in clinic what the following stages of its studying testify to: in 1962 it was established for
shchitny effect monkey And. at its introduction (vnutrikozhno) to the people vaccinated against smallpox; in 1966 — 1967 human and - in-terferon used for prevention of flu (intranazalno); in 1973 the positive effect was gained at primeneniya human and - interferon (intramusculary) at patients with a herpes simplex and shingles; in 1974 it was reported about use human and - interferon (intramusculary) in oncological practice at an osteosarcoma; in 1976 positive action was noted And. at a number of infectious viral diseases — a Cytomegaloviral infection (see the Cytomegaly), hepatitis B (see a viral hepatitis)>, a rinovirusny infection (see Rinovirusnaya a disease), the embryopathies (see) caused by a rubella; in 1977 wide use is begun And. in oncological practice concerning a multiple myeloma (see), lymphoma (see), melanomas (see), an osteosarcoma (see), cancer of a neck of uterus (see the Uterus), leukoses (see).
For the first time And. began to use successfully in clinic for prevention of flu in 1966 — 1967 according to V. D. Solovyov's recommendation. In the subsequent the similar preventive effect was reached in SFRYu. Widely apply And. at treatment of herpetic damages of eyes and to lay down. action was noted as at a superficial, and treelike keratitis (see the Keratitis). Positive takes at treatment are received And. herpes of external genitals (see Herpes). Use And. at shingles led to reduction of frequency of damages of internals, decrease in pain and reduction of frequency of neuralgia. Also positive takes of use deserve attention and-inte_rferon:a at hron. hepatitis B. It was effective And. at treatment and prevention of a dengue (see), arenovirusny diseases (see), the Japanese encephalitis In (see Encephalitis mosquito virus) and some other viral infections.
To the side effects caused And., feverish reaction later 2 — 6 hours after its introduction, and also a passing lymphopenia and thrombocytopenia, temporary oppression of function of marrow, fatigue, etc. belongs.
In onkol. practician I. began to use widely after success achieved at treatment of an osteosarcoma (see). In 1972 H. Strander began to appoint and - interferon at an osteosarcoma of long tubular bones and gained a favorable effect. Success was noted also at treatment by interferon of some other tumors. So, positive takes of use and - iiterfero - on are received at a breast cancer, tumors of a lung, neuroblastomas (in the latter case drugs [5 interferon), papillomas of a throat and bladder were more effective. Good results were received at treatment of leukoses at children: significant increase in duration of remissions was noted.
Despite rather small term of use And. in onkol. to practice, it is possible to make the certain generalizations characterizing effect of this drug. At use And. the tumor (papilloma of a throat and bladder, a melanoma) can regress completely or from inoperable to turn in resectable (a breast cancer, an osteosarcoma); use And. before operation blocks distribution of tumor cells that reduces danger of a meta s'gazirovaniye; And. promotes reduction of number of metastasises and their regression; efficiency And. increases at simultaneous introduction of tsitostatik (see. Antineoplastic means).
Analysis of routes of administration And. in onkol. to practice demonstrates that to replace local use native or partially cleared And. ny introduction, and also introduction to the spinal channel of more purified drug I comes intramuscular, intravenous, vnutris a sloe of l. Also the tendency to increase in a dose of drug is accurately traced: from 30 Ltd companies to 10 million. Piece on 1 injection, and on a nek-eye to data, a minimal effective dose And. makes
2 million. Piece on 1 kg of the weight (weight) of the recipient that with a weight of the person (75 kg) makes 150 million. Pieces. At introduction of such quantity And. its concentration in blood serum reaches 160 PIECES in 1 ml. However optimum concentration it is offered to consider 500 PIECES in 1 ml of blood serum. Achievement of this concentration requires introduction of 300 million. Piece of interferon, i.e.
4 million. Piece on 1 kg of body weight.
Intramuscular and continuous intravenous administration And. allows to support a certain level it in blood (at peroral or an intranaza flax introduction And. practically does not get to blood). Without repeated introduction And. quickly disappears from blood and collects in various bodies: heart, muscles, lungs, spleen, liver and kidneys. The most high level And. it is noted in kidneys: its concentration in them is at least 10 times higher, than in other bodies. And. easily passes through capillaries of renal balls, undergoing almost full readsorbtion, and collapses in lysosomes of tubular cells. Absence And. in urine allows to consider kidneys the main place of its destruction and removal from an organism. And. almost does not get from blood into cerebrospinal liquid, into a brain and eyes.
Receiving drugs I. high extent of cleaning and high concentration from natural producers (leukocytes. fibroblasts) is complex and expensive process, in time to-rogo a significant amount of a starting material is lost. So, but to data of laboratory of biosynthesis of interferon of scientific research institute of epidemiology and microbiology of N. F. Gamale of the USSR Academy of Medical Sciences, during the receiving drug I. with activity 3 * 106 PIECES on 1 mg of protein are lost to 40% initial by I. Perspektivny receiving recombinant and - interferon by means of a genetically engineered method is. Comparative study human natural and - and R-interferonov and recombinant and - the interferon received from bacteria allowed to come to conclusion that all of them possess quite comparable antiviral and antiproliferativ-ache activity. Moreover, use recombinant and - interferon assumes a possibility of receiving its drugs with the set ratios antiklegoch-ache also antiviral activity that, undoubtedly, will have important practical value as will allow to receive drugs I. certain purpose (antiviral, antineoplastic, etc.).
Bibliography: E r sh about in F. I. Is also new oh and t with to and y A. S. Interferon and its inductors, M., 1980; With e m e N about in B. F., To and at l e D. G. N and Skillies and I. G. N, Cellular and molecular bases of virus-induced immunity, M., 1982; With about ~ l about in e in V. D. and B e to t e m of in T. A. Interferona's ditch in the theory and practice of medicine, M., 1981; X e with and Ya. E N. Cytogenetic bases of products and effect of human interferon, Usp., sovr. biol., t. 93, century 3, page 363, 1982, bibliogr.; Dziewanowska Z. E. and., P e s t k a S. The human interferons, Med. Res. Rev., v. 2, p. 325, 1982, bibliogr.; Interferon therapy, Techn. rep. ser., N 676, Geneva, 1982; Stewart II W. E. The interferon system, Wien — N. Y.,
V. D. Solovyov, I. G. Balangding.
Bibliogr. Krmolyepa 3, Century. Antibiotics, Interferon, Bacterial polysaccharides, M., 1968, bibliogr.; E r-sh about in F. I. Mekhanizm of effect of interferon, Usp. sovr, biol., t. 77, No. 3, page 369, 1974; Interferon, under the editorship of A. A. Smoro-dintsev and A. Smorodintsev Ave, L., 1970; With about l about in e in V. D. and Bektem and-r about in T. A. Interferon in the theory and practice of medicine. M, 1970, bibliogr.; Physiology of viruses, interferona and in-terferonogena, under the editorship of M. P. Chumakov, M. 1971; Interferons and interferon inducers, ed. by N. B. Finter, N. Y., 1973; V i 1 with e k J. Interferon, Wien — N. Y., 1969, bibliogr.
T. A. Bektemirov.