Mayr S, Walz C R, Angele P, Hernandez-Richter T, Chaudry I H, Loehe F, Jauch K W, Angele M K
Dept. of Surgery, Klinikum Grosshadern, Ludwig-Maximilians Univ., Marchioninistr. 15, 81377 Munich, Germany.
J Appl Physiol (1985). 2006 Aug;101(2):448-53. doi: 10.1152/japplphysiol.00166.2006. Epub 2006 Apr 13.
Several studies indicate that cell-mediated immune responses, i.e., macrophage (MPhi) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after trauma-hemorrhage in male mice. Testosterone has been shown to be responsible for the depression of MPhi cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic MPhi was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in MPhi from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss.
多项研究表明，细胞介导的免疫反应，即巨噬细胞（MPhi）细胞因子释放能力、肌球蛋白重链（MHC）II类（Ia）表达等，在雄性小鼠创伤性出血后受到抑制。已证明睾酮是雄性小鼠创伤性出血后MPhi细胞因子反应受抑制的原因。通过MHC II类进行抗原呈递在启动和维持细胞介导的和体液免疫反应中起关键作用。然而，睾酮在创伤性出血后对MHC II类是否有任何影响仍不清楚。为了研究这一点，雄性C3H/HeN小鼠在创伤（中线剖腹术）和出血（Hem；血压35±5 mmHg持续90分钟并复苏）或假手术前2周进行去势或假去势。此后4小时，使用流式细胞术测量MHC II类（Ia）表达。结果表明，创伤性出血后雄性小鼠腹膜和脾脏MPhi上的MHC II类（Ia）表达显著受到抑制。然而，预先去势可防止创伤性出血后腹膜和脾脏MPhi上MHC II类（Ia）表达的降低。去势对假去势小鼠MPhi中的MHC II类（Ia）表达没有影响。因此，睾酮会降低雄性小鼠创伤性出血后腹膜和脾脏MPhi上的MHC II类（Ia）表达。由于MHC II类对于充分的免疫反应是必需的，我们的结果表明，使用氟他胺等药物耗尽雄性性激素或阻断雄激素受体可能通过在创伤和严重失血后维持MHC II类（Ia）表达来预防免疫抑制。
