Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol 281: C1131-C1138, 2001;
0363-6143/01 $5.00
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Vol. 281, Issue 4, C1131-C1138, October 2001

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

Markus W. Knöferl1, Doraid Jarrar1, Martin K. Angele1, Alfred Ayala1, Martin G. Schwacha2, Kirby I. Bland2, and Irshad H. Chaudry2

1 Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903; and 2 Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35394

Recent studies indicate that immune responses in proestrus females are maintained after trauma-hemorrhage but markedly depressed in ovariectomized females under such conditions. The current study tested the hypothesis that the decreased estrogen levels after ovariectomy are responsible for this immune depression. To study 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 mice received either 17beta -estradiol (E2; 100 µg/25 g body wt) or vehicle subcutaneously during resuscitation. Immune cells were isolated 24 h thereafter. Splenocyte proliferation and interferon-gamma , interleukin (IL)-2, and IL-3 release were significantly depressed after trauma-hemorrhage in vehicle-treated mice, whereas these functions were maintained in E2-treated mice. Peritoneal macrophage IL-1beta and IL-6 release and splenic macrophage IL-6 and IL-12 release were also significantly depressed in vehicle-treated mice after trauma-hemorrhage, and release of these cytokines was restored by E2 treatment. In summary our findings indicate that the depressed splenic and peritoneal immune responses after trauma-hemorrhage can be normalized by a single dose of E2. Thus estrogen appears to be the causative factor in the maintenance of immunocompetence in females after trauma-hemorrhage, and its administration to ovariectomized or postmenopausal females should be helpful in preventing immune depression under such conditions.

T lymphocyte; macrophage; inflammation; immunosuppression; gender


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