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(Journal of Leukocyte Biology. 2001;70:887-895.)
© 2001 by Society for Leukocyte Biology

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

Kelly A. N. Messingham*,{dagger},{ddagger}, Scott A. Heinrich*,{dagger} and Elizabeth J. Kovacs*,{dagger},{ddagger},§

* Department of Cell Biology, Neurobiology, and Anatomy,
{dagger} The Burn and Shock Trauma Institute,
{ddagger} Alcohol Research Program,
§ Department of Surgery, and
|| Immunology and Aging Program, Loyola University Medical Center, Maywood, Illinois

Correspondence: Elizabeth J. Kovacs, Ph.D., Building 110, Room 4221, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153. E-mail: ekovacs{at}lumc.edu

This study examined whether estrogen treatment can improve immunity in male mice after combined ethanol and burn injuries. 17ß-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-{kappa}B (NF-{kappa}B) activation in injured mice. There were no changes in cellular NF-{kappa}B or I{kappa}B{alpha} protein expression or I{kappa}B{alpha} phosphorylation at serine 32. Taken together, these studies suggest that estrogen treatment of injured male mice improves cellular immunity through direct modulation of NF-{kappa}B activation.

Key Words: cytokine • NF-{kappa}B • monocyte/macrophage • hormone • ethanol • burn




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