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Am J Physiol Cell Physiol 277: C35-C42, 1999;
0363-6143/99 $5.00
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Vol. 277, Issue 1, C35-C42, July 1999

Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage

Martin K. Angele, Markus W. Knöferl, Martin G. Schwacha, Alfred Ayala, William G. Cioffi, Kirby I. Bland, and Irshad H. Chaudry

Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903

Studies indicate that macrophage immune responses in males are depressed after trauma-hemorrhage, whereas they are enhanced in females under such conditions. Nonetheless, the involvement of male and female sex steroids in this gender-dependent dimorphic immune response after trauma-hemorrhage remains unclear. To study this, male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5alpha -dihydrotestosterone (DHT), 17beta -estradiol, or a combination of both steroid hormones for 14 days before soft tissue trauma (i.e., laparotomy) and hemorrhagic shock (35 ± 5 mmHg for 90 min followed by adequate fluid resuscitation) or a sham operation. Twenty-four hours later the animals were killed, plasma was obtained, and Kupffer cell and splenic and peritoneal macrophage cultures were established. For DHT-treated mice, we observed significantly decreased releases of the proinflammatory cytokines interleukin 1beta (IL-1beta ) and IL-6 by splenic macrophage (-50 and -57%, respectively) and peritoneal macrophage (-51 and -52%, respectively) cultures after trauma-hemorrhage compared with releases by cultures of cells from mice subjected to a sham operation; in contrast, responses of splenic and peritoneal macrophage cultures from other groups subjected to trauma-hemorrhage did not change significantly. In addition, only DHT-treated animals exhibited increased Kupffer cell IL-6 release (+634%). The release of IL-10 in DHT-treated hemorrhaged animals was increased compared with that in sham-operated animals but was decreased in estrogen-treated mice under such conditions. These results suggest that male and female sex steroids exhibit divergent immunomodulatory properties with respect to cell-mediated immune responses after trauma-hemorrhage.

gender; immune depression; Kupffer cells; shock


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