[Inhibitor of the action of swine leukocyte interferon]. / Ingibitor deistviia svinogo leikotsitarnogo interferona.

Studies on the antagonists of interferon effect ("stimulon", "TAI", "blocker", "antiinterferon") formed under the influence of viruses and mitogens as well as those found in noninfected tissues deal largely with their blocking effect on the antiviral activity of interferon. Previously we had found an inhibitor of antiviral effect in preparations of human cadaverous and swine leukocyte interferons. This paper presents the results of studies on some physico-chemical properties of an inhibitor of the effect of swine leukocyte interferon and its antiproliferative activity. The inhibitor is resistant to the effect of nucleases and lyophilization, manifests limited heterospecificity towards interferons and cell cultures, has marked antiproliferative activity in different cell cultures including those of tumor origin.

[Study of the safety, reactogenicity, and allergenicity of swine leukocyte interferon in experiments on animals and observations of volunteers]. / Izuchenie bezvrednosti, reaktogennosti i allergennosti svinogo leikotsitarnogo interferona v éksperimentakh na zhivotnykh i v nabliudeniiakh na dobrovol'tsakh.

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.

[Concentration of heterogeneous leukocyte interferon]. / Kontsentrirovanie geterogennogo leikotsitarnogo interferona.

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.

[Method of increasing the activity of a preparation of human cadaver leukocyte interferon]. / Sposob povysheniia aktivnosti preparata chelovecheskogo leikotsitarnogo kadavernogo interferona.

A simple method for increasing the activity of human leukocyte interferon is described. It is based on the removal from the native preparation of a presumed inhibitor of antiviral effect followed by condensation of the resulting fractions by thin-canal cells TCF-10 of an Amicon apparatus. With this method of concentration there was no loss of the general initial antiviral activity. Depending on the titer of the initial interferon and the condensation degree, the native interferon was concentrated 32--350-fold. The resulting concentrated interferon preparation is nontoxic, areactogenic, safe in animal trials and may be recommended for trials as a therapeutic-prophylactic means in various viral diseases.

[Differences in the properties of the interferons produced by the leukocytes of healthy persons and of cancer and leukemia patients]. / Razlichiia v svoistvakh interferonov, produtsiruemykh leikotsitami krovi zdorovykh liudei, bol'nykh rakom i leikozom.

In vitro production of interferon by blood leukocytes from patients with lymphosarcoma, lymphogranulomatosis, leukemia, cancer tumours, pneumonia, as well as by leukocytes of mice with Rauscher leukemia, and mice in the condition of hyporeactivity to interferon inducer was studied. Alongside with quantitative differences in interferon production, biological differences in the properties of interferons produced of normal and sick humans and animals were revealed. The biological differences consist in that the interferon produced by leukocytes from cancer and leukemia patients interacting with homologous cell culture is conducive to more rapid formation of resistance to the indicator virus than the interferon produced by normal leukocytes. Thus, resistance of the homologous cell culture to the infection with the indicator vesicular stomatitis virus developed within 1--2 hours after contact with leukocyte interferon from patients and only within 5--6 hours after contact with that of normal subjects. This finding is not specific for cancer and leukemia, as the same was observed with specimens from patients with pneumonia and from mice hyporeactive to interferon inducer. It is suggested that patients with cancer and leukemia have a state of interferon hyporeactivity.

[Relationship between manifestation of hyporeactivity (tolerance) in interferon production and the presence of a viral interferon inductor in the cells of the tolerant animal]. / Izuchenie sviazi mezhdu proiavleniem giporeaktivnosti (tolerantnosti) v interferonogeneze i nalichiem v kletkakh tolerantnogo zhivotnogo virusnogo induktora interferona.

Experiments revealed parallelism between the duration of the main manifestations of the hyporeactivity phenomenon (tolerance) in interferon induction and the duration of detection of a masked infection with the inducer virus (Newcastle disease virus) in peritoneal exudate cells of tolerant mice. It was also shown that after contact of chick fibroblasts with a dose of interferon which completely inhibited replication of vesicular stomatitis virus infecting the cells this virus was found in the cells in the masked form. Persistence of a virus interferon inducer in the masked form appears to play a significant role in the mechanism of tolerance as well as creation in the interferon-treated cells of conditions for masking viruses infecting these cells.

[Reasons for lowered resistance to Krebs 2 ascitic carcinoma in mice in a state of hyporeactivity (tolerance) to a viral interferon inducer]. / Prichiny snizheniia rezistentnosti k astsitnoi kartsinome Krebs-2 u myshei v sostoianii giporeaktivnosti (tolerantnosti) k virusnomu induktoru interferona

Decreased resistance to Krebs-2 ascitic carcinoma was demonstrated in mice which were in the state of hyporesponsiveness (tolerance) to virus interferon inducer (NDV) and increased resistance of the control mice to transplantation of tolerant carcinoma cells. Manifestations of tolerance in peritoneal and carcinoma cells were shown to be identical: interferon production and reproduction of vesicular stomatitis virus were inhibited, the number of viable cells was reduced, masked infection with NDV was detected, and the activity of cell enzymes was similarly changed. It is assumed that cellular manifestations of tolerance are the cause of reduced resistance of tolerant mice to ascitic carcinoma.

[Clinical study of the therapeutic effectiveness of an ointment consisting of swine leukocytic interferon]. / Klinicheskoe izuchenie lechebnoi éffektivnosti mazi, soderzhashchei svinoi leikotsitarnyi interferon.

The ointment containing pig leukocytic interferon had a pronounced therapeutic effect in herpetic affections of the face skin and genitalia. It prevented eruption, shortened the period of its healing and eliminated subjective sensations. The therapeutic effect was observed in 265 (87.7 per cent) out of 302 patients with recurring Herpes simplex treated with ointment.

[Trial of the safety, reactivity and therapeutic effectiveness of an ointment containing swine leukocytic interferon]. / Ispytanie bezvrednosti, reaktogennosti i lechebnoi éffektivnosti mazi, soderzhashcheí svinoi leikotsitarnyi interferon.

An ointment containing porcine leucocytic interferon (PLI) with the use of lanolin as the base and addition of human serum albumin for stabilization of the antiviral activity and Tris-or Hepes-buffer solutions for stabilization of the medium pH value was studied. The trials on volunteers with herpetic affections of the face and genitalia showed absolute safety of the drug, its areactivity and sufficiently high therapeutic efficacy as compared to an ointment containing human leucocytic interferon. The positive effect was observed in 52 out of 78 patients. On the basis of these data the PLI may be recommended for further clinical trials.

[Inactivation of the inductor virus (Newcastle disease virus) during the isolation of porcine leukocyte interferon]. / Inaktivatsiia virusa-induktora (virus bolezni N'iukasla) v protsesse polucheniia svinogo leikotsitarnogo interferona.

The use of the routine method for inactivation of the inductor virus by acidification of interferon to pH 2.0 resulted in a significant decrease in the antiviral activity of pig leukocytic interferon, since the preparation was highly sensitive to changes in the pH values. The use of 0.1 per cent solution of formalin provided complete inactivation of the virus. The antiviral activity of interferon treated with formalin was on an average 5 times higher than that of the preparation incubated at pH 2.5-2.6. Precipitation of pig interferon with polyethylene glycol promoted both increasing of the titers of the antiviral activity of the preparation and elimination of the formalin residues from it. Interferon prepared with this procedure was not toxic in tissue cultures, had no side effects when applied to the eye mucosa and was absolutely harmless when administered to animals. It was shown that inactivation of the inductor virus with formalin was in principle possible in human leukocytic interferon.