Dehydroepiandrosterone - An inexpensive steroid hormone that decreases themortality due to sepsis following trauma-induced hemorrhage

Background: Recent studies suggest that male sex steroids play a role in pr oducing immunodepression following trauma-hemorrhage. This notion is suppor ted by studies showing that castration of male mice before trauma-hemorrhag e or the administration of the androgen receptor blocker flutamide followin g trauma-hemorrhage in noncastrated animals prevents immunodepression and i mproves the survival rate of animals subjected to subsequent sepsis. Howeve r, it remains unknown whether the most abundant steroid hormone, dehydroepi androsterone (DHEA), protects or depresses immune functions following traum a-hemorrhage. In this regard, DHEA has been reported to have estrogenic and androgenic properties, depending on the hormonal milieu. Objective: To determine whether administration of DHEA after trauma-hemorrh age has any salutary or deleterious effects on immune responses, and whethe r it improves the survival of animals subjected to subsequent sepsis. Design: Male C3H/HeN mice underwent laparotomy tie, trauma-induced) and hem orrhagic shock (blood pressure, 35 +/- 5 mm Hg for 90 minutes) followed by fluid resuscitation, or sham operation. The animals then received 100 mg of DHEA (4 mg/kg) or propylene glycol thereafter referred to as vehicle). At 24 hours after trauma-hemorrhage and resuscitation, the animals were killed and blood, spleens, and peritoneal macrophages were harvested. Splenocyte proliferation and interleukin (IL) 2 release and splenic and peritoneal mac rophage IL-1 and IL-6 release were determined. In a separate set of experim ents, sepsis was induced by cecal ligation and puncture at 48 hours after t rauma-hemorrhage and resuscitation. For those studies, the animals received vehicle, a single 100-mu g dose of DHEA, or 100 mu g/d DHEA for 3 days fol lowing hemorrhage and resuscitation. Survival was monitored for 10 days aft er the induction of sepsis. Results: Administration of DHEA restored the depressed splenocyte and macro phage functions at 24 hours after trauma-hemorrhage. Moreover, daily admini stration of DHEA for 3 days significantly increased the survival of animals subjected to subsequent sepsis (P = .01). Conclusion: The finding that DHEA markedly improves the depressed immune fu nctions and survival of animals subjected to subsequent sepsis suggests tha t shortterm treatment with DHEA after trauma-hemorrhage is a safe and novel approach for Preventing immunodepression and for decreasing the mortality rate due to subsequent sepsis.