17 beta-Estradiol normalizes immune responses in ovariectomized females after trauma-hemorrhage

Recent studies indicate that immuneresponses in proestrus females are maintained after trauma-hemorrhagebut markedly depressed in ovariectomized females under such conditions.The current study tested the hypothesis that the decreased estrogenlevels after ovariectomy are responsible for this immune depression. Tostudy this hypothesis, ovariectomized female CBA/J mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 ± 5 mmHg for 90 min, then resuscitated) or sham operation. The micereceived either 17-estradiol (E2; 100 µg/25 g body wt) or vehiclesubcutaneously during resuscitation. Immune cells were isolated 24 h thereafter. Splenocyte proliferation and interferon-, interleukin(IL)-2, and IL-3 release were significantly depressed aftertrauma-hemorrhage in vehicle-treated mice, whereas these functions weremaintained in E2-treated mice. Peritoneal macrophage IL-1 and IL-6release and splenic macrophage IL-6 and IL-12 release were alsosignificantly depressed in vehicle-treated mice after trauma-hemorrhage, and release of these cytokines was restored by E2treatment. In summary our findings indicate that the depressed splenicand peritoneal immune responses after trauma-hemorrhage can benormalized by a single dose of E2. Thus estrogen appears to be thecausative factor in the maintenance of immunocompetence in femalesafter trauma-hemorrhage, and its administration to ovariectomized orpostmenopausal females should be helpful in preventing immunedepression under such conditions.