Ma Choudhry

ARE THE PROTECTIVE EFFECTS OF 17??-ESTRADIOL ON SPLENIC MACROPHAGES AND SPLENOCYTES AFTER TRAUMA-HEMORRHAGE MEDIATED VIA ESTROGENRECEPTOR (ER)-?? OR ER-???

The depression in cell-mediated immune function following trauma-hemorrhage is shown to be restored by 17 -estradiol (E2) administration. However, it remains unknown which of the two estrogenreceptors, (ER)or ER, plays the predominant role in mediating the beneficial effects of E2. Female B57BL/J6 ER/ 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 g/25 g) or ERagonist propyl pyrazole triol (PPT; 50 g/25 g) following traumahemorrhage. 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 TNFand 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 E2and PPT-treated WT mice, the release of cytokines by macrophages and splenocytes in E2and 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. J. Leukoc. Biol. 79: 000–000; 2006.