[The interferon-induced and antiviral activities of dipeptides].

Five phosphodipeptides were synthesized; two of them (H-Lys-Ala(P) and H-Pro-Ala(P) had interferon-induced activity. These dipeptides at millimolar concentrations (10(-4)) and 10(-5) M) induced the synthesis of late (40-hour) interferon in human peripheral blood lymphocytes. The dipeptides H-Lys-Ala(P) and H-Pro-Ala(P) showed a protective antiviral activity in in vivo studies when singly intraperitoneally administered to mice 2 hours before inoculation with murine encephalomyocarditis virus.

[Interferon-inducing properties of dry birch bark extract and its effect on experimental infection caused by hepatitis C virus].

The interferon-inducing activity of dry birch bark extract containing betulin and its effect on hepatitis C virus (HCV)-induced infection were studied in the cultured cells. All samples of the extract induced increased interferon (IFN) production when it was orally and intraperitoneally administered. The dose-dependence of the production of IFN showed a direct relation of the extract to interferon induction. There is strong evidence for that the extract can decrease the antigenic and infective activity of HCV in both in vitro experiments and HCV-induced infection in mice. The preventive effect of the extract was found in both the HCV-infected cell cultures and the HCV-infected mice.

[Antiviral and anti-stress activity of the gamma-L-glutamyl-histamine and its derivatives]. / Protivovirusnaia i antistressornaia aktivnost' gamma-L-glutamilgistamina i ego analogov.

Effect of gamma-L-glutamylhistamine gamma-L-Glu-HA and some of its derivatives on the state of nonspecific resistance and antiviral activity was studied using experimental models of influenza virus and herpes simplex virus infections. Activities of natural killer (NK) cells and interferon (IFN) system were measured. The model of physical-emotional stress in mice was used. It was shown that the gamma-L-Glu-HA derivative II can prevent totally or substantially a decrease in the NK activity. This agent also prevents inhibition of synthesis of alpha- and gamma-IFN during the post-stress period. The gamma-L-Glu-HA derivatives II, III, and VII increased the mice resistance to influenza virus type A/Aichi at low infection dose (10LD50). The derivative II showed its protective effect even at high dose of pathogen (100LD50). However, this gamma-L-Glu-HA derivative was virtually ineffective under harsh experimental conditions. Thus, a number of gamma-L-Glu-HA derivatives tested in this work demonstrated immunomodulation activity. These agents were able to normalize parameters of nonspecific immunity. They exerted a pronounced antiviral effect against influenza virus but were virtually ineffective against encephalitis in mice caused by herpes simplex virus, type 1. Of all tested agents, gamma-L-Glu-HA derivative II was found to be the most promising.

[Effect of amyxin--a domestic analog of tilorone--on characteristics of interferon and immune status of man]. / Vliianie amiksina--otechestvennogo analoga tilorona--na pokazateli interferonovogo i immunnogo statusa cheloveka.

The influence of amyxin, the Russian oral analog of tilorone, on the human interferon and immune status has been evaluated. As revealed by this investigation the administration of amyxin has produced a rise in the content of serum interferon, an increase in the capacity of leukocytes and lymphocytes for synthesizing alpha- and gamma-interferon, the activation of NK and phagocytizing cells of peripheral blood. No essential influence of amyxin on the amount of B and T lymphocytes, their subpopulations and the levels of the main classes of immunoglobulins has been established.

[Evaluation of the immune and interferon status of children infected with herpes simplex virus and living in areas with increased radiation background]. / Otsenka immunnogo i interferonovogo statusov detei, infitsirovannykh virusom prostogo gerpes, prozhivaiushchikh na territorii s povyshennym radiatsionnym fonom.

Virological and immunological examinations were carried out in 52 children aged 4 to 15 living at the Bryansk district territories contaminated with radionuclides after the Chernobyl accident. The persistence of herpes simplex virus (HSV) in the blood was detected by indirect immunofluorescence in 90% of children, in 10% it was confirmed by the virus isolation in vitro in a cell culture. Specific antibodies to HSV-1 and HSV-2 were detected by enzyme immunoassay in 100% examinees, in 50% their titers surpassed those in the control group. Study of the cell-mediated immunity reactions showed increased spontaneous lymphocyte blastogenesis in 46%, a functional defect of lymphocytes upon their nonspecific stimulation with PHA mitogen and increased antigen-dependent capacity of cells to proliferation in 45%, and increased levels of circulating immune complexes in the blood and a tendency to increase of the IgG and decrease of the IgA levels in the blood serum. In addition, a quantitative imbalance was revealed in the T-cell population. Study of interferon production revealed a reduced capacity of blood lymphocytes to produce gamma-interferon and an increased production of alpha-interferon by leukocytes, as well as an increased level of circulating interferon in the serum. These data indicate a decrease of the immune status due to radiation and HSV infection.

[Study of an experimental herpesvirus infection during irradiation]. / Izuchenie éksperimental'noi gerpesvirusnoi infektsii v usloviiakh oblucheniia.

Ionising radiation (IR) in experiment is a factor aggravating herpes virus infection in mice. A direct relationship exists between radiation dose, survival and mean life span of mice. Immunofluorscent test demonstrates that there are similar location and dynamic intensity of fluorescence of herpes simplex virus (HSV) antigen in hepatocytes and cerebral cells from both infected and irradiated then infected animals. Radiation does not influence virus reproduction. In irradiated and infected mice IR suppressed functional activity of immunocompetent cell populations responsible for immunity. This suppression was accompanied with some disorders in immunological parameters: enhancement of spontaneous reactivity of splenocytes, reduction of titres of antibodies against HSV in the serum and of antigen- and mitogen-induced splenocyte ability to proliferate. The splenocytes and bone marrow cells in irradiated and infected mice are able to produce alpha- and gamma-interferons. However, the dynamics of interferon production was different evidencing radiation- and HSV-induced damage to macrophage-reticuloendothelium.

[Arbidole--a new drug for prevention of influenza and acute viral respiratory infections in children]. / Arbidol--novoe sredstvo dlia profilaktiki grippa i ostrykh respiratornykh virusnykh infektsii u detei.

The antiviral drug arbidole reduces influenza and acute respiratory diseases (ARD) in children by 1.5-2 times when given in a dose of 0.1-0.2 g 2-3 or 5 times a week, by making influenza and ARD milder and decreasing their duration by 1.4-2.8 days. Unified regimens for prophylactic use of arbidole in influenza and ARD in children and adults are proposed.

[The antitumor action of double-stranded interferon inducers (larifan, ridostin) and reaferon in an experiment]. / Protivoopukholevoe deistvie dvuspiral'nykh induktorov interferona (larifana, ridostina) i reaferona v éksperimente.

Interferon inducers larifan and rhidostin, and reaferon were shown to exert an inhibiting antitumor effect manifested in the prolongation of the incubation period, decrease of the size of tumors, and longer survival of the animals. The maximal anti-tumor and immunomodulating effect was obtained by combined use of preimmunization with tumor cells and simultaneous administration of reaferon or interferon inducers, larifan and rhidostin. Larifan was also shown to have a greater antitumor activity than rhidostin. Larifan, however, was maximally active only in combination combination with vaccination using syngeneic cells of the virus-induced tumor. In this case levels of alpha and gamma interferons were 2-4 times higher than normally.

[Experience with the combined treatment of recurrent herpes using larifan and a herpetic vaccine]. / Opyt kombinirovannogo lecheniia retsidiviruiushchego gerpesa larifanom i gerpeticheskoi vaktsinoi.

Interferon inductor larifan used parenterally was combined with herpetic vaccine to treat severe recurrent herpes in 32 patients. This combination therapy started at initiation of herpetic infection activation and resulted in amelioration of the clinical symptoms of the recurrence, a more favourable course of the disease due to stimulation of the interferon system and natural killer activity. In combination the above modalities proved more effective than in monotherapy.

[Levels of interferon-dependent enzymes in urticaria patients, connected with frequent viral infections]. / Urovni interferonzavisimykh fermentov u bol'nykh krapivnitsei, sviazannoi s chastymi virusnymi infektsiiami.

27 patients with relapsing and giant urticaria accompanied by multiple general respiratory viral infection and herpetism were studied during acute and remittent steps as compared with 13 healthy volunteers. 10 patients were treated with reaferon. Elevated rates of circulating interferon and interferon-dependent enzymes as well as a decreased ability of leukocytes and lymphocytes to produce alpha- and gamma-interferons were detected in these patients. Anomalous reactions of the interferon system were found in the patients with urticaria and general viral respiratory infection simultaneously with impairments of the immunity response: discorrelation between rates of interferon-dependent enzymes and circulating interferon. The course of interferon therapy within 5 days using recombinant alpha 2-interferon did not obviate these deteriorations, although activity of 2-5A synthetase tended to decrease down to the level observed in healthy persons.

[Antitumor effect of the Soviet recombinant alpha2-interferon (reaferon) under experimental conditions]. / Protivoopukholevyi éffekt otechestvennogo preparata rekombinantnogo alpha2-interferona (reaferona) v éksperimente.

The antitumor and immunomodulating effect of reaferon was demonstrated in Syrian hamsters bearing tumors induced by cells transformed by HSV-1 DNA (the EH/A-44 strain). The animals received a total of 5 X 10(3) IU/ml of reaferon. In combined use of a lysate of destroyed tumor cells (DTC) and reaferon the best results were obtained with regard to an increase in the latent period of tumor development, differences in the tumor size, and increase in the survival time of the experimental animals as compared with the control group. In 75% of the animals given DTC and reaferon no tumors were observed up to 113 days. The above data suggest that reaferon may be recommended for combined therapy in malignant diseases where the etiologic factors might be viruses of the herpes group.

[Interferon status and the activity of dsRNA-dependent enzymes in volunteers and influenza patients receiving human recombinant alpha 2-interferon (reaferon)]. / Interferonovyi status i aktivnost' dsRNK-zavisimykh fermentov u dobrovol'tsev i bol'nykh grippom liudei, poluchavshikh chelovecheskii rekombinantnyi al'fa 2-interferon (reaferon).

The national recombinant preparation of alpha 2-interferon (reaferon) after intramuscular inoculation in a daily dose of 3 X 10(6) units/ml to human volunteers was found in the blood serum within 1-2 hours. In 85% of the subjects given the preparation, a 2-8-fold rise in interferon titers in the blood serum and in 64% an increase in interferon leukocyte reaction (ILR) by the 5th day after the beginning of the treatment were observed. In the examined influenza patients given the preparation, interferon circulation in the blood serum, increased ILR and 2-5A synthetase enzyme levels were demonstrated. Tests for interferon of the blood sera of patients given reaferon by inhalation revealed no significant rise in its level, in contrast to cases with reaferon intramuscular injections. It is assumed that the immunomodulating effect of the preparation given by inhalation is mediated through the hypothalamus. Thus, parameters of the interferon system may be corrected by administration of reaferon.

[Evaluation of dipyridamole efficacy as an agent for preventing acute respiratory viral diseases]. / Otsenka éffektivnosti dipiridamola kak sredstva profilaktiki ostrykh respiratornykh virusnykh zabolevanii.

The epidemiological effectiveness of a low molecular interferon inducer, dipyridamole, as a means of prevention of influenza and ARD was studied in a double-blind epidemiological trial in a period of seasonal rise of ARD (Dec., 26, 1984-March 13, 1985). A statistically significant decrease of ARD incidence (1.91-fold) in the experimental group was confirmed by the results of serological studies and titrations of serum interferon in paired sera collected before the prevention and 10 days after its termination in selected subgroups from the experimental and control groups. The results indicate that the use of dipyridamole may be effective for mass prevention of influenza and ARD.

[Natural killers and interferon in complicated influenza and other acute respiratory viral diseases in children]. / Estestvennye killery i interferon pri oslozhnennom grippe i drugikh ostyrkh respiratornykh virusnykh zabolevaniiakh u detei.

The results of the study on the functional activity of natural killers (NK) and serum interferon in 118 children ranging in age from 3 months to 5 years suffering from influenza and other acute respiratory viral diseases complicated with croup, pneumonia, and obstructive syndrome (66 children with influenza, 21 with parainfluenza, 16 with adenovirus infection, and 15 with respiratory syncytial virus diseases) are presented. The control group consisted of 22 normal children. Decreased NK activity was demonstrated in the acute period of all ARVD but was more marked in adenovirus disease and complications with pneumonia, bronchiolitis, obstructive syndrome. While in hospital, children with low interferon titres developed a new acute viral disease more frequently or their principal disease was complicated with pneumonia. The detection of NK cell inhibition in some patients with ARVD complicated with pneumonia, bronchiolitis and decreased serum interferon levels in these patients are considered as indications for administration of immunotherapy (levamisole, zixorin, cathergen).

[Antiproliferative effect of interferon inducers]. / Antiproliferativnyi éffekt induktorov interferona.

The antiproliferative effect of clinically promising interferon inducers, phage f2 ambermutant dsRNA, polyguacyl, tiloron, Tash-4, was demonstrated in Raji lymphoblastoid cells. Concentrations of the inducers producing death of 48-66% of Raji cells were determined to be: for dsRNA, 200 micrograms/ml; polyguacyl, 400 micrograms/ml; tiloron, 100 micrograms/ml; Tash-4, 200 micrograms/ml, which corresponded to the antiproliferative effect of 200 units/ml of alpha-interferon and 40 units/ml of gamma-interferon. No antiproliferative effect was observed at dsRNA, polyguacyl, and Tash-4 concentrations below 100 micrograms/ml. None of the inducers exerted the antiproliferative effect on the selected concentrations on normal human diploid cells. The results obtained explain the antitumorigenic effect of these inducers, demonstrated previously.