Effects of long-term estrogen treatment on IFN-gamma, IL-2 and IL-4 gene expression and protein synthesis in spleen and thymus of normal C57BL/6 mice.

Estrogens have been shown to markedly modulate the immune system. One mechanism by which estrogens could modulate the immune system is by regulating cytokines, an aspect not well-studied thus far. To address this issue, normal C57BL/6 orchiectomized mice were given estrogen and its effects on selected cytokines, interferon-gamma (IFN-gamma), interleukin 2 (IL-2) and IL-4 in lymphocytes from a developmental organ (thymus) and a mature lymphoid organ (spleen) examined. Estrogen significantly increased IFN-gamma and IL-2 mRNA in concanavalin-A (Con-A) activated thymocytes, splenic lymphocytes, and in enriched splenic T cells. Estrogen had no marked effect on IL-4 mRNA. While estrogen increased IFN-gamma mRNA in Con-A activated unseparated splenic lymphocytes and enriched splenic T cells, a numerical increase in IFN-gamma was noticed only in the supernatants of Con-A activated unseparated splenic lymphocytes, but not in enriched splenic T cells. This suggests that for optimal secretion of IFN-gamma in estrogen-treated mice, co-stimulatory signals from antigen presenting cells are needed. Gender differences in IFN-gamma and IL-2 mRNA were also evident. Con-A activated splenic lymphocytes from gonadal-intact, untreated female had a pattern of numerical increase in IFN-gamma mRNA, and IFN-gamma and IL-2 protein levels compared to their male counterparts. Taken together, our data suggests that estrogens regulate the expression of cytokines, which could account in part, for the gender differences in immune capabilities.