Published online before print March 10, 2006

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(Journal of Leukocyte Biology. 2006;79:1173-1180.)
© 2006 by Society for Leukocyte Biology

Are the protective effects of 17ß-estradiol on splenic macrophages and splenocytes after trauma-hemorrhage mediated via estrogen-receptor (ER)- or ER-ß?

Frank Hildebrand^*,1, William J. Hubbard^*, Mashkoor A. Choudhry^*, Bjoern M. Thobe^*, Hans-Christoph Pape and Irshad H. Chaudry^*,2

^* Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham; and
Trauma Department, Hannover Medical School, Germany

²Correspondence: Center for Surgical Research, University of Alabama at Birmingham, GO94 Volker Hall, 1670 University Boulevard, Birmingham, AL 35294-0019. E-mail: Irshad.chaudry{at}ccc.uab.edu

ABSTRACT

The depression in cell-mediated immune function following trauma-hemorrhage is shown to be restored by 17ß-estradiol (E2) administration. However, it remains unknown which of the two estrogen-receptors, (ER)- or ER-ß, plays the predominant role in mediating the beneficial effects of E2. Female B57BL/J6 ER-ß^–/– transgenic mice [knockout (KO)] and corresponding ovariectomized wild-type (WT) mice were subjected to laparotomy and hemorrhagic shock (35.0±5.0 mmHg for 90 min) and treated with E2 (50 µg/25 g) or ER- agonist propyl pyrazole triol (PPT; 50 µg/25 g) following trauma-hemorrhage. Four hours after resuscitation, systemic cytokine concentrations and cytokine release by splenocytes and splenic macrophages were determined by cytometric bead array. Trauma-hemorrhage resulted in a significant increase in plasma tumor necrosis factor (TNF-), interleukin (IL)-6, and IL-10. In contrast, the release of these cytokines by splenic macrophages was decreased significantly in WT and KO animals. Administration of E2 or PPT following trauma-hemorrhage produced a significant reduction in systemic TNF- and IL-6 concentrations in WT and KO mice. Although the suppression in the productive capacity of these cytokines following trauma-hemorrhage by macrophages and splenocyte was also prevented in E2- and PPT-treated WT mice, the release of cytokines by macrophages and splenocytes in E2- and PPT-treated KO mice was not restored to the levels observed in sham animals. These findings collectively suggest that both receptors appear to play a significant role in mediating the immunoprotective effects of E2 in different tissue compartments following trauma-hemorrhage.

Key Words: shock • immune response • injury • sex hormones • propyl pyrazole triol • knockout

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