Testosterone and/or low estradiol: Normally required but harmful immunologically for males after trauma-hemorrhage
Testosterone and/or low estradiol: Normally required but harmful immunologically for males after trauma-hemorrhage
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DOI：
10.1097/00005373-199801000-00007
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发表时间：
1998-01-01
影响因子：
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通讯作者：
Chaudry, IH
中科院分区：
文献类型：
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作者：
Angele, MK;Ayala, A;Chaudry, IH
背景：以往的研究表明，严重出血后，雄性小鼠的免疫功能明显受到抑制，而雌性小鼠没有表现出任何抑郁，尽管在软组织创伤和失血性休克前通过去势去雄激素的方法使小鼠的细胞免疫功能受到抑制，但目前尚不清楚睾酮本身是否导致免疫抑制的产生。然后进行软组织创伤(剖腹)和失血性休克(血压35+/-5 mm Hg，持续90分钟)，然后进行充分的液体复苏(脱落血和乳酸林格液)或假手术。两组未处理的雄性C3H/HEN小鼠作为对照：一组失血性休克后复苏，第二组只接受假手术。创伤失血复苏后24小时处死动物，从腹膜和脾脏获取巨噬细胞，并检测其释放白细胞介素1和白介素6的能力。结果：DHT治疗后雌性小鼠体内的DHT水平显著升高，与未治疗的雄性小鼠相当，雌鼠体内的雌二醇水平显著降低，与对照组相当。在赋形剂治疗的雌性小鼠中，创伤失血后巨噬细胞功能没有明显的抑制。相比之下，发生出血的雌性小鼠经睾酮治疗后，脾和腹膜巨噬细胞IL-1和IL-6的产生明显抑制，与出血雄性小鼠的巨噬细胞产生的IL-1和IL-6的水平相当。结论：DHT对雌性小鼠创伤失血后巨噬细胞功能的抑制作用与正常雄性创伤失血小鼠相似。因此，我们认为，高睾酮和/或低雌二醇水平是造成创伤失血后雄性小鼠免疫抑制的原因，睾酮受体阻滞剂，如氟他胺和/或雌二醇的应用，应该是预防男性创伤患者免疫抑制的有效辅助手段。
Background: Previous studies indicate that after severe hemorrhage, immune functions are markedly depressed in males, whereas females do not show any depression, Although androgen depletion by castration of mice before soft-tissue trauma and hemorrhagic shock patients the depression of cell-mediated immunity, it remains unknown whether testosterone per se is responsible for producing immune depression,Methods: Female C3H/HeN mice were pretreated with 5 alpha-dihydrotestosterone (DHT) or vehicle for 20 days, The mice then underwent soft-tissue trauma (laparotomy) and hemorrhagic shock (blood pressure 35 +/- 5 mm Hg for 90 minutes) followed by adequate fluid resuscitation (shed blood and lactated Ringer's solution) or sham operation, Two groups of nontreated male C3H/HeN mice were included as controls: one group was subjected to hemorrhagic shock followed by resuscitation, and the second group underwent only sham operation, At 24 hours after trauma-hemorrhage and resuscitation, animals were killed, macrophages harvested from the peritoneum and spleen, and their ability to release interleukin (IL)-1 and IL-6 was evaluated, Plasma DHT, estradiol, and corticosterone levels were measured by radioimmunoassay.Results: Treatment of female mice with DHT produces a significant increase in DHT levels that was comparable with those seen in nontreated male mice, Alternatively, estradiol levels in female mice were significantly depressed by DHT treatment to levels comparable with those observed in control males, In the vehicle-treated female mice, no depression of the macrophage function was evident after trauma hemorrhage, In contrast, testosterone-treated female mice that had experienced hemorrhage shelved significant depression in splenic and peritoneal macrophage IL-1 and IL-6 production, comparable with the values seen in macrophages from male mice that had experienced hemorrhage,Conclusions: These findings indicate that pretreatment of Female mice with DHT depresses macrophage function after trauma-hemorrhage, which mimics the changes seen in normal male mice subjected to trauma-hemorrhage. We propose, therefore, that high testosterone and/or low estradiol levels are responsible for producing the immune depression in male mice after trauma-hemorrhage, Testosterone receptor blocking agents, e.g., flutamide, and/or estradiol administration should thus be useful adjuncts for preventing immune depression in male trauma patients.