Parlesak A, Diedrich J P, Schäfer C, Bode C
Department of Physiology of Nutrition, Hohenheim University, Stuttgart, Germany.
Infect Immun. 1998 Jun;66(6):2809-13. doi: 10.1128/IAI.66.6.2809-2813.1998.
The ability of polymorphonuclear neutrophils (PMNs) and monocytes (Mphi) to produce reactive oxygen species (ROS) has been related closely to their potential in the killing of microorganisms. Ethanol has been shown to impair the generation of ROS in these phagocytes after stimulation with some immunogens and to increase the susceptibility of alcohol abusers to infectious diseases. As endotoxemia is common in alcohol abusers, we investigated the effect of ethanol (21.7 mmol/liter) on the luminol-amplified chemiluminescence of PMNs and Mphi after endotoxin stimulation and the release of tumor necrosis factor alpha (TNF-alpha) from Mphi. Further, the efficiency of ethanol to inactivate chemically generated ROS was tested. Significant stimulation of ROS release occurred at endotoxin concentrations of 1 ng/ml or higher in both PMNs and Mphi. Ethanol significantly suppressed the formation of ROS in both cell types, the decrease being more pronounced in Mphi (-73. 8%) than in PMNs (-45.7%). The correlations between endotoxin concentration and the amount of released ROS showed a dose-dependent, sigmoidal course. Concentrations of endotoxin necessary for half-maximum stimulation were nearly identical (6 to 8 ng/ml) in both PMNs and Mphi, independent of the presence of ethanol. In contrast to ROS formation, ethanol had no effect on the amount of TNF-alpha produced by endotoxin-stimulated Mphi. Ethanol was shown to be unable to decrease the levels of chemically generated ROS under physiological conditions. Therefore, ethanol cannot be assumed to be an "antioxidative" compound but rather seems to modify processes of endotoxin recognition, intracellular signal transduction, or metabolism.
多形核中性粒细胞（PMNs）和单核细胞（Mphi）产生活性氧（ROS）的能力与其杀灭微生物的潜能密切相关。乙醇已被证明在受到某些免疫原刺激后会损害这些吞噬细胞中ROS的生成，并增加酗酒者对传染病的易感性。由于内毒素血症在酗酒者中很常见，我们研究了乙醇（21.7 mmol/升）对内毒素刺激后PMNs和Mphi的鲁米诺增强化学发光的影响以及Mphi中肿瘤坏死因子α（TNF-α）的释放。此外，还测试了乙醇化学灭活化学产生的ROS的效率。在内毒素浓度为1 ng/ml或更高时，PMNs和Mphi中ROS的释放均受到显著刺激。乙醇显著抑制了两种细胞类型中ROS的形成，Mphi中的下降更为明显（-73.8%），而PMNs中的下降为（-45.7%）。内毒素浓度与释放的ROS量之间的相关性呈剂量依赖性的S形曲线。在PMNs和Mphi中，半最大刺激所需的内毒素浓度几乎相同（6至8 ng/ml），与乙醇的存在无关。与ROS形成相反，乙醇对内毒素刺激的Mphi产生的TNF-α量没有影响。结果表明，在生理条件下乙醇无法降低化学产生的ROS水平。因此，不能认为乙醇是一种“抗氧化”化合物，而似乎是对内毒素识别、细胞内信号转导或代谢过程产生了影响。
