Estrogen restores cellular immunity in injured male mice via suppression of interleukin-6 production

Abstract This study examined whether estrogen treatment can improve immunity in male mice after combined ethanol and burn injuries. 17β-Estradiol [estrogen, given subcutaneously (s.c.)] or oil (control) was administered at 30 min and 24 h postinjury. At 48 h postinjury, ethanol/burn-injured mice demonstrated significant suppression of cellular immunity. Estrogen treatment restored the delayed-type hypersensitivity (P<0.01) and splenocyte-proliferative (P<0.05) responses, reduced macrophage interleukin-6 (IL-6) (P<0.05), and increased survival after bacterial challenge (P<0.01). In vitro neutralization of IL-6, combined with macrophage supernatant experiments, confirmed that the beneficial effects of estrogen treatment were mediated through modulation of macrophage IL-6 production. Moreover, estrogen treatment resulted in a decrease in splenic nuclear factor-κB (NF-κB) activation in injured mice. There were no changes in cellular NF-κB or IκBα protein expression or IκBα phosphorylation at serine 32. Taken together, these studies suggest that estrogen treatment of injured male mice improves cellular immunity through direct modulation of NF-κB activation.