TESTOSTERONE - THE CULPRIT FOR PRODUCING SPLENOCYTE IMMUNE DEPRESSIONAFTER TRAUMA-HEMORRHAGE

Studies indicate that, whereas immune functions in males are depressed , they are enhanced in females after trauma hemorrhage. Moreover, cast ration of male mice (i.e., androgen depletion) before trauma hemorrhag e prevented the depression of cell-mediated immunity. Nonetheless, it remains unknown whether or not testosterone per se is responsible for producing the immune depression. To study this, female C3H/HeN mice (n = 7 animals/group) were pretreated with 5 alpha-dihydrotestosterone (D HT) or vehicle for 19 days, then subjected to laparotomy (e.g., trauma ) and hemorrhagic shock (blood pressure 35 +/- 5 mmHg for 90 min) foll owed by fluid resuscitation or sham operation. Nontreated males underw ent either trauma hemorrhage or sham operation. Twenty-four hours ther eafter, splenocyte immune functions as well as plasma DHT, estradiol, and corticosterone levels were measured. DHT-pretreated females had si gnificantly (P < 0.05) increased DHT levels, comparable to those seen in males. Conversely, estradiol levels in such females were similar to control males. Splenocyte proliferation as well as interleukin-2 and interleukin-3 release were not depressed in vehicle-treated females, w hereas it was in DHT-treated females after trauma hemorrhage, comparab le to hemorrhaged males. Thus high testosterone and/or low estradiol l evels appear to be responsible for producing splenocyte immune depress ion in males after trauma hemorrhage. Agents that block testosterone r eceptors or increase estradiol levels may therefore be helpful in impr oving depressed immune functions in male trauma patients.