Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity
Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity
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DOI：
10.1099/00222615-48-5-425
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发表时间：
1999-05-01
影响因子：
3
通讯作者：
Loria, RM
中科院分区：
文献类型：
--
作者：
Ben-Nathan, D;Padgett, DA;Loria, RM
研究了激素雄烯二醇（雄烯-3 β， 17 β，-二醇；AED）和脱氢表雄酮（5-雄烯-3 β -醇-17-酮；DHEA）对两种致死性细菌感染和内毒素休克的病理生理保护作用。感染包括革兰氏阳性菌（粪肠球菌）和革兰氏阴性菌（铜绿假单胞菌）。两种激素均可保护小鼠免受致死性细菌感染和脂多糖（LPS）攻击，用DHEA治疗致命的铜绿假单胞菌的动物产生43%的保护作用，而AED治疗的保护作用为67%，两种激素也完全保护LD50剂量的E，粪孢感染的动物，同样，LPS攻击的88%死亡率分别通过DHEA和AED治疗降低到17%和8.5%。这两种类固醇的保护作用显示不是直接抗菌，而主要是间接抗毒素反应。DHEA似乎通过阻断毒素诱导的肿瘤坏死因子- α (tnf - α)和白细胞介素-1的病理生理水平产生的机制来调节其保护作用，AED通常比DHEA具有更大的保护作用；然而，在体内和体外，AED的作用与tnf - α抑制无关。提示DHEA和AED均可能参与抗菌免疫抵抗的神经内分泌调节。
The protective effects of the hormones androstenediol (androstene-3 beta, 17 beta,-diol; AED) and dehydroepiandrosterone (5-androsten-3 beta-ol-17-one; DHEA) on the pathophysiology of two lethal bacterial infections and endotoxin shock were examined. The infections included a gram-positive organism (Enterococcus faecalis) and a gram-negative organism (Pseudomonas aeruginosa). Both hormones protected mice from the lethal bacterial infections and from lipopolysaccharide (LPS) challenge, Treatment of animals lethally infected with P. aeruginosa with DHEA resulted in a 43% protection whereas treatment with AED gave a 67% protection, Both hormones also protected completely animals infected with an LD50 dose of E, faecalis, Similarly, the 88% mortality rate seen in LPS challenge was reduced to 17% and 8.5%, by treatment with DHEA and AED, respectively, The protective influences of both steroids were shown not to be directly antibacterial, but primarily an indirect antitoxin reaction. DHEA appears to mediate its protective effect by a mechanism that blocks the toxin-induced production of pathopysiological levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1, AED usually had greater protective effects than DHEA; however, the AED effect was independent of TNF-alpha suppression, both in vivo and in vitro. The data suggest that both DHEA and AED may have a role in the neuro-endocrine regulation of antibacterial immune resistance.