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November 1996

Mechanism of Immunosuppression in Males Following Trauma-Hemorrhage: Critical Role of Testosterone

Author Affiliations

From the Shock and Trauma Research Laboratories, Departments of Surgery (Drs Wichmann, Zellweger, Ayala, and Chaudry and Ms DeMaso), Microbiology (Dr Ayala), and Physiology (Dr Chaudry), Michigan State University, East Lansing; and the Center for Surgical Research, Brown University School of Medicine and Rhode Island Hospital, Providence (Drs Wichmann, Ayala, and Chaudry).

Arch Surg. 1996;131(11):1186-1192. doi:10.1001/archsurg.1996.01430230068012

Objective:  To determine whether male sex steroids contribute to the depression in cell-mediated immunity following trauma-hemorrhage and resuscitation.

Design:  Two weeks before the induction of soft-tissue trauma (2.5-cm midline laparotomy) and hemorrhagic shock (mean [±SEM] blood 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.

Results:  Splenocyte proliferation and splenocyte interleukin-2 and interleukin-3 release were significantly depressed in sham-castrated animals after trauma-hemorrhage. In contrast, these variables in castrated mice after trauma-hemorrhage were similar to those in shamoperated animals. Corticosterone plasma levels were significantly elevated in both trauma-hemorrhage groups compared with those in sham-operated mice. Plasma testosterone levels were undetectable in castrated animals and detectable in sham-castrated mice.

Conclusions:  Castration before soft-tissue trauma and hemorrhagic shock maintains normal immune function in male mice, but sham-castrated male mice show significant immunodepression. The maintenance of immune function by androgen deficiency does not seem to be related to changes in the release of corticosterone. We conclude that male sex steroids are involved in the immunodepression observed after trauma-hemorrhage. Thus, the use of testosterone-blocking agents following trauma-hemorrhage should prevent the depression of immune functions and decrease the susceptibility to sepsis under those conditions.Arch Surg. 1996;131:1186-1192

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