Effects of 17β-estradiol and flutamide on splenic macrophages and splenocytes after trauma-hemorrhage

Since splenic immune functions are depressed in metestrus females following trauma-hemorrhage, we hypothesized that administration of the androgen receptor antagonist flutamide at the onset of resuscitation will maintain the immune function of the spleen following trauma-hemorrhage. Female C57BL6/J mice (metestrus state, 8-12 weeks old), underwent laparotomy and hemorrhagic shock (35.0 +/- 5.0 mm Hg for 90 min) and received 17 beta-estradiol (50 mu g/25 g), flutamide (625 mu g/25 g) or 17 beta-estradiol + flutamide. Four hours after resuscitation, the in vitro productive capacity of different cytokines (TNF-alpha, IL-6, IL-10, and IFN-gamma) by splenic M Phi and splenocytes were determined by flow cytometry. A significantly decreased cytokine production by both splenocytes and splenic M Phi was observed following trauma-hemorrhage compared to shams. Administration of 17 beta-estradiol, flutamide and 17 beta-estradiol + flutamide following trauma-hemorrhage resulted in a significant increase in the in vitro IL-6 release by splenic M Phi. The TNF-alpha productive capacity, however, was only restored by 17 beta-estradiol and 17 beta-estradiol + flutamide administration following trauma-hemorrhage. No significant effect of either treatment was observed with regard to the suppressed splenic M Phi IL-10 release. Anti-CD3 stimulation, administration of 17 beta-estradiol and 17 beta-estradiol + flutamide, but not the administration of flutamide alone resulted in a significant increased release of TNF-alpha, IL-6 and IFN-gamma compared to vehicle-treated animals. No significant effect of either treatment was found on IL-10 productive capacity. These results collectively suggest that flutamide administration following trauma-hemorrhage in females has beneficial effects on splenic immune function. However, flutamide administration in combination with estrogen does not provide any significant, additional effects over 17 beta-estradiol administration alone. (c) 2007 Published by Elsevier Ltd.