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 part, by increased production of interleukin-6 (IL-6). Because 17beta-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.
Gregory
M S
MS
Burn and Shock Trauma Institute, Loyola University Medical Center, 2160 S. First Avenue, Maywood, Illinois 60153, U S A.
Duffner
L A
LA
Faunce
D E
DE
Kovacs
E J
EJ
D000818:Animals; D002056:Burns / Q000276:immunology*; D004958:Estradiol / Q000097:blood / Q000276:immunology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010052:Ovariectomy; D012727:Sex Characteristics; D014599:Uterus / Q000276:immunology
D015850:Interleukin-6; D004958:Estradiol