Dehydroepiandrosterone: a modulator of cellular immunity and heat shock protein 70 production during polymicrobial sepsis
Dehydroepiandrosterone: a modulator of cellular immunity and heat shock protein 70 production during polymicrobial sepsis
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DOI：
10.1007/s00134-007-0851-4
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发表时间：
2007-12-01
影响因子：
38.9
通讯作者：
Schmitz, Daniel
中科院分区：
文献类型：
--
作者：
Oberbeck, Reiner;Deckert, Hanno;Schmitz, Daniel
目的：脱氢表雄酮是一种免疫调节类固醇激素，可提高全身炎症期间的生存率。脱氢表雄酮诱导的热休克蛋白反应的调制可能是一种替代机制，有助于这种激素的有益作用。我们研究了DHEA给药对脓毒症小鼠的生存、细胞免疫功能和HSP-70产生的影响。设计和设置：随机动物研究，一级创伤中心，大学研究实验室。对象：雄性NMRI小鼠。干预措施：对小鼠进行假手术（剖腹手术，CLP）或脓毒症（盲肠结扎和穿孔，CLP），皮下施用或不施用0.9%盐水（CLP，CLP）或20 mg/kg DHEA（CLP/DHEA，CLP/DHEA）。在48小时内监测存活率。在脓毒症发作后48小时监测来自肝、肺和脾的组织提取物中的脾细胞凋亡率（AnnexinV结合）、脾细胞增殖（[H-3]胸苷掺入）、TNF-α血浆浓度（ELISA）和HSP-70浓度（ELISA）。结果：DHEA给药改善了脓毒症小鼠的存活率（78%对50%）。这种作用被脾细胞增殖增加、脾细胞凋亡率降低和TNF-α释放减弱所抵消。此外，增加HSP-70浓度观察到在肺和脾脏的DHEA治疗的脓毒症动物。结论：DHEA治疗降低了脓毒症小鼠的死亡率。这伴随着改善的细胞免疫功能和增强的肺和脾的热休克反应（HSP-70）。需要进一步的研究来证明DHEA治疗动物的存活率提高与观察到的免疫系统改变之间的直接关系。
Objective: DHEA is an immunomodulatory steroid hormone that improves survival during systemic inflammation. A DHEA-induced modulation of heat shock protein response may be an alternative mechanism contributing to the beneficial effects of this hormone. We investigated the effect of DHEA administration on survival, cellular immune functions, and HSP-70 production in septic mice. Design and setting: Randomized animal study, level I trauma center, university research laboratory. Subjects: Male NMRI mice. Interventions: Mice were subjected to sham operation ( laparotomy, LAP) or sepsis (cecal ligation and puncture, CLP) with or without administration of either saline 0.9% ( LAP, CLP) or 20 mg/kg DHEA subcutaneously (LAP/DHEA, CLP/DHEA). Survival was monitored over a 48-h period. Splenocyte apoptosis rate (AnnexinV binding), splenocyte proliferation ([H-3] thymidine incorporation), TNF-alpha plasma concentration ( ELISA), and HSP-70 concentration ELISA) in tissue extracts from liver, lung, and spleen were monitored 48 h after onset of sepsis. Results: DHEA administration improved the survival of septic mice (78% vs. 50%). This effect was paralleled by increased splenocyte proliferation, decreased cellular apoptosis rate of splenocytes, and attenuation of TNF-alpha release. Furthermore, an increased HSP-70 concentration was observed in lungs and spleens of DHEA-treated septic animals. Conclusions: DHEA-treatment decreased the mortality rate of septic mice. This was accompanied by improved cellular immune functions and an augmented heat shock response (HSP-70) of lungs and spleens. Further studies are required to demonstrate a direct relationship between the improved survival and the observed alterations in the immune system in DHEA-treated animals.