Effect of dehydroepiandrosterone on the immune function of mice in vivo and in vitro

Abstract

Dehydroepiandrosterone (DHEA) has anti-inflammatory, anti-oxidant and immune-regulating properties, while the mechanism of DHEA actions remains unclear. The present study aims to investigate the effect and possible mechanism of DHEA on immune function of mice in vivo and in vitro. In vivo, a lipopolysaccharide (LPS)-induced experimental inflammation model was constructed to analyze the regulation of DHEA on anti-oxidative and immune function in ICR mice; In vitro, the effects of DHEA on the biological functions of lymphocytes and macrophages were studied. The results showed that DHEA increased the activity of total antioxidant capacity and superoxide dismutase, while it decreased the level of reactive oxygen species in LPS-induced mice. Meanwhile, DHEA increased the proportion of T lymphocytes and decreased that of B lymphocytes in primary cultured spleen lymphocytes, and markedly enhanced the Th1/Th2 ratio in spleen T lymphocytes. Furthermore, DHEA significantly increased the Th1 type cytokine (IL-2 and IFN-α) and decreased the Th2 type cytokine (IL-4 and IL-10) levels in LPS-induced mice or in primary cultured spleen T lymphocytes. In addition, DHEA improved the phagocytic ability, enhanced the NO production and increased the iNOS activity in peritoneal macrophages. Our data indicates that DHEA increases the macrophages function via improving NO content and up-regulating TNF-α expression levels; and it evoked a Th1 immuno-response and repressed a Th2 immuno-response through promoting a shift in Th1/Th2 balance toward Th1-dominant immunity in vivo and in vitro. These results provide substantial evidence on the mechanism of DHEA-mediated immune function and the efficient protection against infectious and inflammatory response in animals and humans.