MECHANISM OF IMMUNOSUPPRESSION IN MALES FOLLOWING TRAUMA-HEMORRHAGE -CRITICAL ROLE OF TESTOSTERONE

Objective: To determine whether male sex steroids contribute to the de pression in cell-mediated immunity following trauma-hemorrhage and res uscitation. Design: Two weeks before the induction of soft-tissue trau ma (2.5-cm midline laparotomy) and hemorrhagic shock (mean [+/-SEM] bl ood pressure, 35+/-5 mm Hg), male C3H/HeN mice were castrated or sham castrated. Following trauma-hemorrhage, the mice were resuscitated and killed 24 hours thereafter to obtain whole blood and the spleen. Resu lts: Splenocyte proliferation and splenocyte interleukin-2 and interle ukin-3 release were significantly depressed in sham-castrated animals after traumahemorrhage. In contrast, these variables in castrated mice after trauma-hemorrhage were similar to those in sham-operated animal s. Corticosterone plasma levels were significantly elevated in both tr auma-hemorrhage groups compared with those in sham-operated mice. Plas ma testosterone levels were undetectable in castrated animals and dete ctable in sham-castrated mice. Conclusions: Castration before soft-tis sue trauma and hemorrhagic shock maintains normal immune function in m ale mice, but sham-castrated male mice show significant immunodepressi on. The maintenance of immune function by androgen deficiency does not seem to be related to changes in the release of corticosterone. We co nclude that male sex steroids are involved in the immunodepression obs erved after trauma-hemorrhage. Thus, the use of testosterone-blocking agents following trauma-hemorrhage should prevent the depression of im mune functions and decrease the susceptibility to sepsis under those c onditions.