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 mecha nism by which estrogens could modulate the immune system is by regulating c ytokines, an aspect not well-studied thus far. To address this issue, norma l C57BL/6 orchiectomized mice were given estrogen and its effects on select ed cytokines, interferon-gamma (IFN-gamma), interleukin 2 (IL-2) and IL-4 i n lymphocytes from a developmental organ (thymus) and a mature lymphoid org an (spleen) examined. Estrogen significantly increased IFN-gamma and IL-2 m RNA in concanavalin-A (Con-A) activated thymocytes, splenic lymphocytes, an d 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 sple nic lymphocytes and enriched splenic T cells, a numerical increase in IFN-g amma was noticed only in the supernatants of Con-A activated unseparated sp lenic 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 IF N-gamma and IL-2 mRNA were also evident. Con-A activated splenic lymphocyte s from gonadal-intact, untreated female had a pattern of numerical increase in IFN-gamma mRNA, and IFN-gamma and TL-2 protein levels compared to their male counterparts. Taken together, our data suggests that estrogens regula te the expression of cytokines, which could account in Dart, for the gender differences in immune capabilities. (C) 2001 Academic Press.