title: Role of Cytokines in Immunomodulatory Effects of Polyprenyl Phosphate: New Generation of Antiviral Drugs.
abstract: 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).
authors.affiliation: Gamaleya Institute for Epidemiology and Microbiology, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Alexander V.
authors.initials: AV
authors.lastname: Pronin
authors.forename: Sergei V.
authors.initials: SV
authors.lastname: Ozherelkov
authors.forename: Alexander N.
authors.initials: AN
authors.lastname: Narovlyansky
authors.forename: Leonid L.
authors.initials: LL
authors.lastname: Danilov
authors.forename: Sergei D.
authors.initials: SD
authors.lastname: Maltsev
authors.forename: Anna V.
authors.initials: AV
authors.lastname: Deyeva
authors.forename: Ekaterina A.
authors.initials: EA
authors.lastname: Grigorieva
authors.forename: Alexander V.
authors.initials: AV
authors.lastname: Sanin