Administration of female sex steroids in males after trauma-hemorrhage has salutary effects on the depressed immune responses.
Randomized laboratory experiment.
Male C3H/HeN mice were subjected to midline laparotomy and hemorrhagic shock (35 ± 5 mm Hg for 90 minutes, then resuscitation) or sham operation and received subcutaneous 17β-estradiol (40 µg/kg body weight) or corn oil vehicle at the beginning of resuscitation.
Main Outcome Measures
At 24 hours after hemorrhage, the animals were killed and plasma 17β-estradiol and IL-6, splenocyte interleukin (IL) 2, IL-3, and IL-10 production as well as splenic and peritoneal macrophage IL-1β, IL-10, and IL-6 release were measured.
Splenocyte IL-2 and IL-3 release were significantly depressed after hemorrhage in vehicle-treated mice (P<.05, analysis of variance). Treatment with 17β-estradiol after hemorrhage led to the restoration of splenocyte IL-2 and IL-3 release. The depressed proinflammatory cytokine (IL-1 and IL-6) release seen in splenic and peritoneal macrophages was restored in the 17β-estradiol–treated hemorrhage group. In contrast, the sustained release of the anti-inflammatory cytokine IL-10 by splenocytes and splenic and peritoneal macrophages in vehicle-treated mice after hemorrhage was decreased in 17β-estradiol–treated mice. The increase in circulating IL-6 levels after hemorrhage was significantly attenuated in 17β-estradiol–treated mice. Although administration of 17β-estradiol increased plasma 17β-estradiol levels by approximately 100% in sham as well as hemorrhage groups, improved immune responses were seen only in posthemorrhage 17β-estradiol–treated mice. There was no adverse effect of 17β-estradiol treatment in the sham or posthemorrhage groups.
Since administration of a single dose of 17β-estradiol in males after trauma-hemorrhage restores the immune functions and decreases circulating levels of IL-6, hormones with estrogenic properties should be considered as safe and novel therapeutic agents for restoring the immune responsiveness in male trauma victims.