Влияние Гамапрена на продукцию регуляторных цитокинов при экспериментальной флавивирусной инфекции у мышей

Abstract

Phosphorylated polyprenols-based medicines are known to inhibit the reproduction of viruses in vitro, as well as exert therapeutic effect in experimental viral infections and viral diseases of pets. The aim of the study was to assess the effect of Gamapren (GP), the active ingredient of which are phosphorylated polyprenols isolated from mulberry leaves, on the production of key regulatory cytokines (CT) ― interferon-gamma (IFN-γ), interleukin-10 (IL-10) and interleukin-12 (IL-12) in experimental infection caused by tick-borne encephalitis virus (TBEV), Absettarov strain, in mice. The levels of CT production in the serum of mice was determined by ELISA using commercial sets of firms «Genzyme» and «BioSource» (USA) according to the instructions for use. Infection of mice with TBEV led to the development of acute lethal infection. In the control life expectancy was 8.4 days. Under the action of GP, which was administered 3 and 2 days before infection of mice TBEV, life expectancy increased to 10.9 days, and in the case when GP was administered 3 days before and simultaneously with TBEV, life expectancy increased to 12.5 days. In TBEV-infected mice an increase in serum levels of IFN-γ was recorded on day 4 and 7. On the contrary, GP stimulated the production of IFN-γ at 48 hours. When GP was inoculated simultaneously with TBEV, the level of IFN-γ in blood serum increased on the 3rd and 7th day. When studying the content of IL-10 and IL-12 in the serum of mice, it was shown that in intact mice GP stimulated the content of IL-12 at all stages of the experiment, except for 4 and 10 days. The level of IL-10 did not change throughout the experience, not exceeding the control. To the contrary, in TBEV-infected mice stimulation of IL-12 production was revealed att the 5th (in the second half of the incubation period), 9-th and 10-th day (the period of TBE clinical signs) after infection. The level of IL-10 was increased by 1-st (12.6-fold), 7th and 8th day after infection, tick-borne encephalitis virus (5.6 and 7.2-fold, respectively). In mice simultaneously inoculated with GP and TBEV, the most significant stimulation of IL-12 production was observed at 4th, 5th, 9th and 10th days. IL-10 production was found only at day 3 following GP and TBEV inoculation. At all other stages of the study, IL-10 levels did not exceed the benchmark. Thus, GP inoculated to the TBEV-infected mice stimulates the early production of IFN-γ and IL-12, which may act as one of the key mechanisms of GP antiviral activity. Viruses have the ability to disrupt the balanced development of Th1/Th 2 immune response needed to form an effective antiviral immunity, and GP stimulating the production of key cytokines providing a balanced formation of Th1 and Th2 immune response is able to restore this necessary balance. This property of GP in combination with direct antiviral action, apparently, also provides protection against a virus infection.