Stimulation of Th2 response by high doses of dehydroepiandrosterone in KLH-primed splenocytes

Although dehydroepiandrosterone (DHEA) has long been considered as a precursor for steroid hormones, it has also been shown to have regulatory effects in immune homeostasis. We have examined the effect of high DHEA doses on T cell proliferation, differentiation, and cytokine secretion patterns following stimulation with mitogens and soluble antigens. DHEA profoundly inhibited T cell receptor-mediated T cell proliferation in the upstream of IL-2R signaling. Addition of DHEA to KLH-primed splenocytes stimulated Th2 response, indicated by an increase of IL-4 or a decrease of IFN-gamma production in the cultures. Further studies showed that DHEA enhanced IL-4, but inhibited IL-12-mediated T cell proliferation and IL-12 production in antigen-presenting cells (APCs). Our data demonstrated that supraphysiologic levels of DHEA favored Th2 immune responses in vitro by inhibition of IL-12 production from APCs and/or stimulation of Th2 proliferation during the interactions of T cells with APCs.