Danenberg H D, Alpert G, Lustig S, Ben-Nathan D
Department of Virology, Israel Institute for Biological Research, Ness-Ziona.
Antimicrob Agents Chemother. 1992 Oct;36(10):2275-9. doi: 10.1128/AAC.36.10.2275.
Recent reports have demonstrated an immunomodulating activity of dehydroepiandrosterone (DHEA) different from that described for glucocorticoids. The present study was designed to test DHEA's activity in endotoxic shock and to investigate its effect on endotoxin-induced production of tumor necrosis factor (TNF). Mortality of CD-1 mice exposed to a lethal dose of lipopolysaccharide (LPS; 800 micrograms per mouse) was reduced from 95 to 24% by treatment with a single dose of DHEA, given 5 min before LPS. LPS administration resulted in high levels of TNF, a response that was significantly blocked by DHEA, both in vivo and in vitro. DHEA treatment also reduced LPS-induced increments in serum corticosterone levels, a parameter considered not to be mediated by TNF. In another experimental model, mice sensitized with D-galactosamine, followed by administration of recombinant human TNF, were subjected to 89% mortality rate, which was reduced to 55% in DHEA-treated mice. These data show that DHEA protects mice from endotoxin lethality. The protective effect is probably mediated by reduction of TNF production as well as by effecting both TNF-induced and non-TNF-induced phenomena.
近期报告显示，脱氢表雄酮（DHEA）具有不同于糖皮质激素的免疫调节活性。本研究旨在测试DHEA在内毒素休克中的活性，并研究其对内毒素诱导的肿瘤坏死因子（TNF）产生的影响。给予致死剂量脂多糖（LPS，每只小鼠800微克）的CD-1小鼠，在LPS注射前5分钟给予单剂量DHEA治疗后，死亡率从95%降至24%。给予LPS后会导致TNF水平升高，而DHEA在体内和体外均能显著阻断这一反应。DHEA治疗还降低了LPS诱导的血清皮质酮水平升高，而血清皮质酮水平升高这一参数被认为不是由TNF介导的。在另一个实验模型中，用D-半乳糖胺致敏后再给予重组人TNF的小鼠，死亡率为89%，而经DHEA治疗的小鼠死亡率降至55%。这些数据表明，DHEA可保护小鼠免受内毒素致死作用。其保护作用可能是通过减少TNF的产生以及影响TNF诱导和非TNF诱导的现象来介导的。
