Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage?

Hypothesis: Administration of female sex steroids in males after trauma-hem orrhage has salutary effects on the depressed immune responses. Design: Randomized laboratory experiment. Interventions: Male C3H/HeN mice were subjected to midline laparotomy and h emorrhagic shock (35 +/- 5 mm Hg for 90 minutes, then resuscitation) or sha m operation and received subcutaneous 17 beta-estradiol (40 mu g/kg body we ight) or corn oil vehicle at the beginning of resuscitation. Main Outcome Measures: At 24 hours after hemorrhage, the animals were kille d and plasma 17 beta-estradiol and IL-6, splenocyte interleukin (IL) 2, IL- 3, and IL-10 production as well as splenic and peritoneal macrophage IL-1 b eta, IL-10, and IL-6 release were measured. Results: Splenocyte IL-2 and IL-3 release were significantly depressed afte r hemorrhage in vehicle-treated mice (P < .05, analysis of variance). Treat ment with 17 beta-estradiol after hemorrhage led to the restoration of sple nocyte IL-2 and IL-3 release. The depressed proinflammatory cytokine (IL-1 and IL-6) release seen in splenic and peritoneal macrophages was restored i n the 17 beta-estradiol-treated hemorrhage group. In contrast, the sustaine d release of the anti-inflammatory cytokine IL-10 by splenocytes and spleni c and peritoneal macrophages in vehicle-treated mice after hemorrhage was d ecreased in 17 beta-estradiol-treated mice. The increase in circulating IL- 6 levels after hemorrhage was significantly attenuated in 17 beta-estradiol -treated mice. Although administration of 17 beta-estradiol increased plasm a 17 beta-estradiol levels by approximately 100%;, in sham as well as hemor rhage groups, improved immune responses were seen only in posthemorrhage 17 beta-estradiol-treated mice. There was no adverse effect of 17 beta-estrad iol treatment in the sham or posthemorrhage groups. Conclusion: Since administration of a single dose of 17 beta-estradiol in m ales after trauma-hemorrhage restores the immune functions and decreases ci rculating levels of IL-6, hormones with estrogenic properties should be con sidered as safe and novel therapeutic agents for restoring the immune respo nsiveness in male trauma victims.