Estrogen mediates the sex difference in post-burn immunosuppression

Previous studies in our laboratory have demonstrated that cell-mediated immune function was suppressed in female, but not male. mice at 10 days after burn injury and was mediated, in pare, by increased production of interleukin-6 (IL-6). Because 17 beta-estradiol (E-2) influences immune function after trauma and the hormone is known to regulate IL-6 production, the effect of E-2 on immune function after thermal injury was examined. Increased circulating concentrations of E-2 corresponded with suppressed delayed-type hypersensitivity (DTH) and splenocyte-proliferative responses, and increased circulating concentrations of IL-6 in female mice after burn. Ovariectomy restored the suppressed DTH response and decreased IL-6 concentrations, and administration of exogenous E-2 to both ovariectomized females and intact male mice resulted in a suppressed DTH response. In addition, in vitro treatment with E-2 suppressed splenocyte proliferation in a macrophage-dependent manner and enhanced macrophage production of IL-6. These results strongly suggest that the sex difference in cell-mediated immunity 10 days after burn injury is mediated by altered concentrations of E-2, which in turn modulate key macrophage-derived immunoregulatory cytokines.