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Swine blood leukocytes have first been found capable of producing interferon the antiviral activity in human cells of which is comparable to that of native human leukocyte interferon. The influence of various factors on production of porcine leukocyte interferon active in human cells were studied. Thus, when serum was substituted with MAF in the medium used for leukocyte cultivation the titer of the produced interferon increased 4--16-fold and the content of protein impurities in the preparation decreased 10-fold or more. Marked individual interferon-producing capacity of blood leukocytes from different swine and seasonal variations in the level of this capacity were established. The optimal conditions for porcine leukocyte interferon production are: the use of leukocytes in the first few hours after bleeding of the animals; leukocyte concentration in the medium 10 million cells per 1 ml; medium 199 with 10% MAF; New-castle disease virus as interferon inducer in a dose of 10--100 CPD50 per cell. Priming of leukocytes with interferon enhanced their interferon-synthesizing capacity 2--8-fold. This new source of interferon production is readily available, and interferon is useful for public health and veterinary needs.

The results of comparative experiments in guinea pigs sensitized with human and porcine leukocyte interferon are presented. The animals were inoculated either intracardially or intradermally with the appropriate interferon 18-24 days after a single intramuscular or a single subcutaneous interferon injection, the latter with Freund adjuvant. The results of anaphylaxy reaction and dermal reaction permit a conclusion of lower allergenicity of porcine interferon than of human one. Daily intranasal inoculation of both porcine and human interferon for 5 days did not produce sensitization of guinea pigs, and three daily intranasal inoculations for 5 days of porcine interferon to 22 human volunteers produced no untoward systemic or local reactions nor allergic reaction to intradermal inoculation of these volunteers with porcine interferon 24 hours after termination of intranasal administration. These results justify limited clinical trials of therapeutic and prophylactic effectiveness of porcine interferon in viral ARD, using the intranasal route of interferon administration.

The nucleated cells of the bone marrow of mouse, rat, guinea pig, chick, cattle and humans proved to be capable of producing interferon in vitro following induction with the Newcastle disease virus. The production of interferon by these cells was characterized by high stability. The bone marrow interferon was not inferior in its activity to the corresponding interferon prepared with the blood leukocytes or splenic cells.

A single dose of actinomycin-D (2.5 mg/kg body wt) reduced the interferon formation 16-fold in comparison with control; as to the antibody production - it was completely abolished. Hydrocortiosone (100 mg/kg) also diminished the interferon production 16-fold, but had no effect on the production of antibodies against the virus. The effect of hydrocortisone on the antiviral immunity was similar to that of the antilymphocytic serum, whereas the action of actinomycin-D resembled the effect of the X-ray irradiation or imuran. The data obtained were consistent with the suggestion on the heterogeneity of cells, participating in the interferon production in the organism.

A comparative study of different methods for concentration of porcine leukocyte interferon active in human cells was carried out. Ultrafiltration in an apparatus TCF-10 was found to be the most effective method of concentration by which preparations of porcine interferon showing antiviral activity up to 1 X 10(6) IU/ml were obtained. The total antiviral activity of concentrated interferon was twice as high as that of the native preparation. This increase of the total initial activity is due to the removal in the process of concentration of an inhibitor of antiviral activity which was isolated and concentrated. The concentrated preparation of porcine leukocyte interferon is now undergoing trials in veterinary and medicine.

Bone marrow cells from suddenly dying people can produce interferon in response to incoulation of an inducer. The interferon obtained in bone marrow cells did not differ by its properties from the reference preparation. the lots of bone marrow interferon which had been prepared were not inferior in the antiviral activity to leukocyte interferon or were even superior to it. It is suggested that bone marrow cells be used for preparation of human interferon.

A comparative study of biological properties of natural and plasmid human interferons was carried out. Natural and leukocyte interferons: alpha (induced by Newcastle disease virus) and gamma (induced by staphylococcal enterotoxin A) as well as natural fibroblastic beta interferon induced by poly(I) X poly(C) were studied in comparison with plasmid interferons alpha-F and alpha-F/D obtained from recombinant bacteria. Antigenic determinants of plasmid interferons alpha-F and alpha-F/D were found to be identical with those of natural and alpha-interferon of man and to differ from those of natural human alpha- and beta-interferons. Both plasmid interferons demonstrated the kinetics of development of the state of resistance to viruses in a human diploid cell culture typical of alpha-interferon but not of gamma-interferon from human leukocytes. Plasmid and natural alpha-interferons have similar anticellular activity for human tumor HeLa cells, similarly activate natural human killer cells and are similarly stabilized in the presence of 0.01 M lantan chloride. All these data permit a conclusion that plasmid human interferons alpha-F and alpha-F/D are analogous and close to the total preparation of natural alpha-interferon from human leukocytes. On the other hand, the range of cells sensitive to the antiviral effect of alpha-F and alpha-F/D interferons is wider than for leukocyte alpha-interferon, and stability on storage and heating is higher.

Administration of high doses of imuran had no significant effect on the multiplication of influenza A/PR8 and Coxsackie A6 viruses. However, the serum levels of interferon and antibody were completely suppressed. Peripheral leukocytes of mice given imuran produced no interferon in vitro. These data suggest that the impairment of formation of the antiviral immunity factors resulting from the administration of high doses of immunosuppressants, such as used during the graft rejection crises, could serve as one of the main causes facilitating viral infections in the course of the transplantation therapy. The results could be of practical importance for the development of the optimal immunosuppression schedules during the organ transplantation.

The effect of exogenous leukocyte interferon on the course of chronic oncornavirus infection of lymphoblastoid J-96 cells chronically producing type B virus was studied. By means of radio-isotope analysis and electron microscope examinations it was shown that upon long-term passage of the cells (18-34 passages) in the presence of interferon (10 units/ml) the process of virion formation in the cells was inhibited 2.0-4.4-fold and virus budding to a lower extent (1.6-2.7-fold). Interferon exerted no inhibiting effect on the formation of intracytoplasmic virions of type A. The employment of KC-test showed the oncornavirus produced by J-96 cells in the presence of interferon to have retained its biological activity, being able to induce synthesis of the indicator KC cells. Examination of the cell membranes by electrophoresis in polyacryl amide gel showed that interferon contributed to accumulation of glycoproteins with high molecular weights (115 000, 100 000 and 68 ooo daltons) in this cell fraction. Simultaneously the experimental cells were found to have 2-3-fold increased amount of inter-species group-specific antigen of Mason-Pfizer virus. The mechanism of action of interferon on multiplication of J-96 cell oncornavirus is discussed.

Chick embryo cultures treated with interferon yielded a biologically active RNA which, upon inoculation into chick embryo cells, created an antiviral condition in them. The level of vesicular stomatitis virus reproduction in such cells was 2-30% of that observed in the cells treated with control RNA. The maximum activity of the experimental RNA was seen 3 hours after the treatment with interferon.

Intraperitoneal injection of various preparations of mouse interferons (L cell tissue culture interferons, concentrated or partly purified, and also serum interferon) significantly inhibited the development of Ehrlich's ascites carcinoma in randombred mice. In view of comparatively low activity of serum interferon, the effect of normal mouse serum on the tumour development and its action on L cell tissue culture interferon was investigated. It was shown that normal mouse serum inhibits the action of L cell tissue culture interferon and promotes the development of Ehrlich's ascites carcinoma.

Production of different kinds of interferon in imported media (medium 199, Eagle's medium) greatly impedes the organization of large-scale interferon production in this country. The search for national substitutes of these media is important therefore. This paper deals with a comparative study of the use of national aminopeptide and hemohydrolysate preparations for interferon production. It was shown that substitution of serum with BAF in preparations of human and swine interferon increased their activity 2- and 4-fold, respectively, and the amount of protein was reduced 10-fold. Specimens of interferons produced with the addition of AP were less effective because the amount of protein increased 4-20-fold while the antiviral activity increased insignificantly. The most effective were interferon preparations obtained with hemohydrolysate medium. Their activity being similar, the amount of protein in interferon samples increased 11/2-2-fold only. Thus, aminopeptide and hemohydrolysate can effectively substitute medium 199 for production of leukocyte human and swine interferon.

This study is a continuation of the investgation of the influence of endogenous and exogenous interferon on influenza infection. Influenza B virus strains, both laboratory and fresh isolates, were found to be poor interferon inducers in contrast to influenza A virus strains. The study also showed that influenza B virus strains not only induced endogenous interferon poorly but were also resistant to exogenous interferon. This evidence points to marked differences of the investigated influenza B virus strains not only induced endogenous interferon poorly but were also resistant to exogenous interferon. This evidence points to marked differences of the investigated influenza B virus strains from influenza A virus strains which further indicates their peculiar nature.

Inoculation into irradiated (800--850 r) mice of syngeneic bone marrow cells treated with mRNA for interferon (mRNA-If) obtained from chick cells induced with UV-irradiated Newcastle disease virus was accompanied by the appearance in the blood of the animals of a substance with the properties of interferon, inhibiting the cytopathic effect of vesicular stomatitis virus in chick embryo cells but not in mouse L cells. Chicken interferon was detected in the blood of the experimental animals for 7--10 days after transplantation of mRNA-If-treated cells.

The results are reported of experimental investigations and epidemiological observations on the use of human leucocyte-produced interferon for influenza prophylaxis. Field trials with interferon were carried out during the outbreak of Hong Kong influenza in the USSR in January and February 1969. These covered about 14 000 people in comparable interferon-and placebo-treated groups and achieved an effectiveness of between 56.3% and 69.2% according to the age-group studied.The importance is shown, not only of artifically introduced interferon, but also of the interferon naturally produced by a subject in response to infection. The degree of such production varies both with each individual's capacity to form interferon and with the capacity of a particular strain of Hong Kong virus to elicit the productive response. The author suggests that isolated virus strains be subdivided into interferon-positive (I+) and interferon-negative (I-) strains according to the presence or absence of this phenotypic character.