Role of Cytokines in Immunomodulatory Effects of Polyprenyl Phosphate: New Generation of Antiviral Drugs.

Immunomodulatory properties of sodium polyprenyl phosphate (PP) were studied in vivo and in vitro. After injection to mice, PP was shown to increase serum levels of TNF-alpha, IL-6, and IFN-gamma. The simultaneous inoculation of tick-born encephalitis virus (TBEV) and PP to mice resulted in earlier serum appearance of IL-6, TNF-alpha and IFN-gamma (at days 1, 2 and 3, respectively) compared with mice which have received PP only. In TBEV-infected mice (not injected with PP) cytokines in serum were registered later - at day 7 after infection. Development of the disease with subsequent death was observed in 100% of infected mice. In contrast, mortality of mice infected with TBEV and simultaneously treated with PP was decreased to 40%. The study of spleen cell proliferative activity in mice injected with PP revealed a modulating effect of the latter. In vitro PP decreased spleen cell and Con A-induced blast proliferation stimulated by Con A and rIL-2 respectively. This effect was dependent upon PP inhibition of IL-2 binding to IL-2 receptors. It was concluded that PP induced early cytokine production (IL-6, TNF-alpha) by cells of monocyte/macrophage origin and, apparently, provided protection of mice against viral infection. Thus, the main properties of PP are the following: absence of the expressed direct effect on cytokine production and co-stimulating effect in combination with a bystander stimulus (in this case - TBEV).