Acute ethanol exposure attenuates pattern recognition receptor activated macrophage functions
Acute ethanol exposure attenuates pattern recognition receptor activated macrophage functions
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DOI：
10.1089/jir.2007.0111
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发表时间：
2008-07-01
影响因子：
2.3
通讯作者：
Kovacs, Elizabeth J.
中科院分区：
文献类型：
--
作者：
Karavitis, John;Murdoch, Eva L.;Kovacs, Elizabeth J.
临床和实验数据都表明，急性乙醇暴露与感染易感性增加以及损伤后发病率和死亡率增加有关。巨噬细胞在先天免疫系统中起着不可或缺的作用，并且在启动适应性免疫系统中很重要。在这项研究中，我们研究了单次体内暴露的巨噬细胞生理相关水平的乙醇（1.2和2.9 g/kg），然后用脂多糖（LPS）或细菌进行体外刺激的效果。我们的研究证实了其他人的工作，即单次给予乙醇抑制了LPS引起的肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和IL-12的产生。在处理后30分钟，乙醇对LPS诱导的细胞因子产生没有影响。相比之下，在3小时，两种剂量的乙醇暴露减少离体TNF-α的生产脾和肺泡巨噬细胞。有趣的是，与对照组（生理盐水处理组）相比，较高剂量的乙醇导致在乙醇给药后3和6小时LPS诱导的TNF-α产生的持续抑制，以及6小时后IL-6和IL-12产生的减少。肺泡巨噬细胞在乙醇处理后3 h表现相似。与盐水处理的动物相比，LPS刺激的TNF-α和IL-6的产生在乙醇给药后3小时减少。用细菌刺激3小时的肺泡巨噬细胞在从给予2.9 g/kg乙醇3小时的小鼠中收获后也显示出TNF-α和IL-6的产生减少。该时间点和高剂量乙醇也导致肺泡巨噬细胞对铜绿假单胞菌的吞噬作用降低。综上所述，我们得出的结论是，乙醇的生理水平的影响是剂量依赖性的，乙醇从循环中清除后的效果，并可以影响多种巨噬细胞功能。
Both clinical and experimental data have linked acute ethanol exposure to increased susceptibility to infection as well as increased morbidity and mortality after injury. Macrophages play an integral role in the innate immune system and are important in priming the adaptive immune system. In this study, we investigated the effect of a single in vivo exposure of macrophages to physiologically relevant levels of ethanol (1.2 and 2.9 g/kg) followed by ex vivo stimulation with lipopolysaccharide (LPS) or bacteria. Our study confirms the work of others showing that a single administration of ethanol suppresses the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-12 in response to LPS. There was no effect of ethanol on LPS induction of cytokine production at 30 min after treatment. In contrast, at 3 h, both doses of ethanol exposure decreased ex vivo TNF-alpha production by splenic and alveolar macrophages. Interestingly, the higher dose of ethanol resulted in sustained suppression of LPS-induced TNF-alpha production at 3 and 6 h after ethanol administration, as well as decreased IL-6 and IL-12 production after 6 h, as compared to control (saline-treated groups). Alveolar macrophages behaved similarly at 3 h after ethanol treatment. LPS-stimulated production of TNF-alpha and IL-6 was reduced at 3 h after ethanol administration, when compared with the saline-treated animals. Alveolar macrophages stimulated for 3 h with bacteria also showed decreased TNF-alpha and IL-6 production after harvested from mice given 2.9 g/kg ethanol for 3 h. This time point and high dose of ethanol also resulted in decreased Pseudomonas aeruginosa phagocytosis by alveolar macrophages. Taken together, we conclude that the effects of physiological levels of ethanol are dose dependent, have effects that last after ethanol is cleared from the circulation, and can affect multiple macrophage functions.