Cytokine Dysregulation and Increased Oxidation Is Prevented by Dehydroepiandrosterone in Mice Infected with Murine Leukemia Retrovirus

Abstract

The effects of murine leukemia retrovirus infection on production of cytokines was investigated in mice fed different doses of dehydroepiandrosterone (DHEA). Young C57BL/6 female mice were injected with LP-BM5 murine retrovirus or were kept as uninfected controls. Two weeks later, each group was divided into subgroups: fed unsupplemented AIN 93 diet as the control, or diets supplemented with 0.02% DHEA (0.9 mg/mouse/day) or 0.06% DHEA (2.7 mg/mouse/day). The uninfected mice supplemented with 0.06% DHEA showed a significant (P < 0.05) increase in interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) production, and hepatic vitamin E levels. Retroviral infection induced severe oxidative stress that was reduced by DHEAS supplementation in retrovirally infected mice. DHEA supplementation prevented the retrovirus-induced loss of cytokines (IL-2 and IFN-gamma) secretion by mitogen stimulated spleen cells. DHEA also suppressed the production of cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by T helper 2 (Th2) cells which were otherwise stimulated by retrovirus infection. Thus, immune dysfunction and increased oxidation induced by murine retrovirus infection were largely prevented by DHEA.