Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage

作者：Martin Kurt Angele, Markus W. Knöferl, Martin G. Schwacha, Alfred Ayala, William G. Cioffi, Kirby I. Bland, Irshad H. Chaudry · 发表于：American Journal of Physiology-Cell Physiology · 年份：1999 · DOI：10.1152/ajpcell.1999.277.1.c35 · 被引用次数：164 · 研究领域：Immune Response and Inflammation、Reproductive System and Pregnancy、Stress Responses and Cortisol

Studies indicate that macrophage immune responses in males are depressed after trauma-hemorrhage, whereas they are enhanced in females under such conditions. Nonetheless, the involvement of male and female sex steroids in this gender-dependent dimorphic immune response after trauma-hemorrhage remains unclear. To study this, male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or a combination of both steroid hormones for 14 days before soft tissue trauma (i.e., laparotomy) and hemorrhagic shock (35 +/- 5 mmHg for 90 min followed by adequate fluid resuscitation) or a sham operation. Twenty-four hours later the animals were killed, plasma was obtained, and Kupffer cell and splenic and peritoneal macrophage cultures were established. For DHT-treated mice, we observed significantly decreased releases of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-6 by splenic macrophage (-50 and -57%, respectively) and peritoneal macrophage (-51 and -52%, respectively) cultures after trauma-hemorrhage compared with releases by cultures of cells from mice subjected to a sham operation; in contrast, responses of splenic and peritoneal macrophage cultures from other groups subjected to trauma-hemorrhage did not change significantly. In addition, only DHT-treated animals exhibited increased Kupffer cell IL-6 release (+634%). The release of IL-10 in DHT-treated hemorrhaged animals was increased co...