Abstract

Studies indicate that androgens are responsible for the depressed splenocyte Th1 cytokine release in males following trauma-hemorrhage. In contrast, female mice maintain their Th1 cytokine release capacity following trauma-hemorrhage. Nonetheless, the effect of male and female sex steroids on Th1 and Th2 cytokine release following trauma-hemorrhage remains unknown. Male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 50α-dihydrotestosterone (DHT), 17β-estradiol (estradiol), or a combination of both steroid hormones, for 14 days prior to soft-tissue trauma (i.e. laparotomy) and hemorrhagic shock (35 ± 5 mmHg for 90 min followed by adequate fluid resuscitation) or sham operation. The animals were sacrificed 24 h later plasma was obtained and splenocytes harvested. Plasma DHT and estradiol levels in treated animals were comparable with intact male and female mice, respectively. A significant depression of splenocyte Th1 cytokines, i.e. IL-2, IFN-γ, was observed in DHT-treated castrated animals, as opposed to maintained Th1 cytokine release in vehicle, estradiol and estradiol/ DHT-treated castrated animals. The release of the anti-inflammatory cytokine IL-10 was markedly increased in vehicle and DHT-treated mice following trauma-hemorrhage, but decreased in estrogen-treated mice. These results suggest that male and female sex steroids differentially affect the release of Th1 and Th2 cytokines following trauma-hemorrhage and should be further studied for their potential to modulate splenocyte function in trauma victims.

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