Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors
Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors
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DOI：
10.1097/01.ccm.0000172278.91959.38
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发表时间：
2005-08-01
影响因子：
8.8
通讯作者：
Angele, MK
中科院分区：
文献类型：
--
作者：
Frantz, MC;Prix, NJ;Angele, MK
Objective.外周血单个核细胞（PBMC）功能障碍发生在腹部大手术后，并与败血症并发症的发生率增加相关。研究表明，脱氢表雄酮（DHEA）可恢复小鼠创伤出血后细胞介导的免疫反应。尽管如此，它仍然是未知的DHEA是否有任何有益的影响，对抑郁的PBMC功能在surgical patients.Design：实验室实验。设置：大学实验室。患者：15例接受腹部大手术。干预：血液样本获得术前和术后2小时。测量和主要结果。在存在或不存在DHEA（10（-10）M、10（-8）M生理浓度、10（-6）M、10（-5）M）的情况下，用33%血浆培养PBMC。在另一组样品中，加入雌激素受体拮抗剂他莫昔芬（10-6 M）。通过酶联免疫吸附试验测定上清液中促炎细胞因子（白细胞介素-1 β、白细胞介素-6和肿瘤坏死因子-α）的释放。腹部手术导致PBMC释放的白细胞介素-1 β和肿瘤坏死因子-α降低。然而，在培养液中加入DHEA可显著提高PBMC释放白细胞介素-1 β和肿瘤坏死因子-α的能力，并刺激PBMC释放白细胞介素-6的能力。浓度为10（-5）M DHEA时，该效应最为显著。DHEA对PBMC细胞因子释放的免疫调节作用可被他莫昔芬完全阻断。相反，DHEA的调节作用通过术后血浆的加入而增强。DHEA刺激腹部大手术后人PBMC的促炎细胞因子释放能力。雌激素受体似乎参与介导DHEA的免疫调节作用。因此，DHEA可能是一个有用的辅助预防免疫抑制手术患者。
Objective. Peripheral blood mononuclear cell (PBMC) dysfunction occurs following major abdominal surgery and correlates with an increased rate of septic complications. Studies have shown that dehydroepiandrosterone (DHEA) restores cell-mediated immune responses after trauma-hemorrhage in mice. Nonetheless, it remains unknown whether DHEA has any salutary effects on depressed PBMC function in surgical patients.Design: Laboratory experiment.Setting: University laboratory.Patients: Fifteen patients undergoing major abdominal surgery.Interventions: Blood samples were obtained preoperatively and 2 hrs postoperatively.Measurements and Main Results. PBMCs were cultured with 33% plasma in the presence or absence of DHEA (10(-10) M, 10(-8) M physiologic concentration, 10(-6) M, 10(-5) M). In an additional set of samples, the estrogen receptor antagonist tamoxifen (10-6 M) was added. The release of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) was measured in the supernatants by enzyme-linked immunosorbent assay. Abdominal surgery resulted in depressed interleukin-1 beta and tumor necrosis factor-alpha release by PBMC. Addition of DHEA to the culture medium, however, significantly improved the release of interleukin-1 beta and tumor necrosis factor-alpha and stimulated the interleukin-6 release capacity of PBMC. This effect was most pronounced for a concentration of 10(-5)M DHEA. The immunomodulatory effect of DHEA on PBMC cytokine release was completely blocked by tamoxifen. In contrast, the modulatory effect of DHEA was enhanced by the addition of postoperative plasma.Conclusions. DHEA stimulates proinflammatory cytokine release capacities of human PBMCs following major abdominal surgery. The estrogen receptor appears to be involved in mediating the immunomodulatory effect of DHEA. Thus, DHEA might be a useful adjunct for preventing immunosuppression in surgical patients.