Mandrekar Pranoti, Catalano Donna, White Bernadette, Szabo Gyongyi
Department of Medicine, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
Alcohol Clin Exp Res. 2006 Jan;30(1):135-9. doi: 10.1111/j.1530-0277.2006.00012.x.
In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor kappaB (NF-kappaB) binding in human monocytes.
Human blood monocytes were isolated by plastic adherence before and after acute alcohol consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)- and superantigen-induced tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1beta, and IL-10 production were then determined in monocytes by ELISA. Nuclear regulatory factor-kappaB activity of monocytes before and after alcohol consumption was estimated by electromobility shift assay and promoter-driven reporter activity. IkappaBalpha was determined by Western blotting in the cytoplasmic extracts.
Eighteen hours after moderate alcohol consumption, we found a significant reduction in monocyte production of inflammatory mediators, TNF-alpha and IL-1beta, in response to LPS or staphylococcal enterotoxin B stimulation. Acute alcohol consumption inhibited LPS-induced DNA binding of the p65/p50 NF-kappaB in monocytes that regulates the expression of both the TNF-alpha and the IL-1beta genes. Consistent with this, acute alcohol treatment (25 mM) significantly reduced LPS-induced activation of an NF-kappaB-driven reporter gene suggesting inhibition of this proinflammatory signaling pathway. Further, LPS-induced IkappaBalpha degradation was not affected by acute alcohol consumption indicating an IkappaBalpha-independent mechanism, as observed earlier in the in vitro acute alcohol studies. In contrast, monocyte production of the anti-inflammatory cytokine, IL-10, was augmented by acute alcohol intake.
Our findings suggest that acute alcohol consumption has dual anti-inflammatory effects that involve augmentation of IL-10 and attenuation of monocyte inflammatory responses involving inhibition of NF-kappaB. These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis.
与长期过量饮酒对肝脏和心血管系统的有害影响相反，适度饮酒，如每天饮用1至2杯酒，对心血管疾病死亡率有益。对于可能导致对动脉粥样硬化性血管疾病至关重要的炎症细胞（如单核细胞）发生改变的饮酒时间长度或饮酒量，人们了解甚少。在此，我们确定急性饮酒对人单核细胞中炎性细胞因子产生和核调节因子κB（NF-κB）结合的体内影响。
在急性饮酒（2毫升伏特加/千克体重）前后，通过塑料贴壁法分离人血单核细胞。然后通过酶联免疫吸附测定法（ELISA）测定单核细胞中脂多糖（LPS）和超抗原诱导的肿瘤坏死因子α（TNFα）、白细胞介素（IL）-1β和IL-10的产生。通过电泳迁移率变动分析和启动子驱动的报告基因活性评估饮酒前后单核细胞的核调节因子-κB活性。通过蛋白质免疫印迹法在细胞质提取物中测定IκBα。
适度饮酒18小时后，我们发现单核细胞在受到LPS或葡萄球菌肠毒素B刺激时，炎性介质TNF-α和IL-1β的产生显著减少。急性饮酒抑制了LPS诱导的单核细胞中p65/p50 NF-κB的DNA结合，而p65/p50 NF-κB调节TNF-α和IL-1β基因的表达。与此一致，急性酒精处理（25毫摩尔）显著降低了LPS诱导的NF-κB驱动的报告基因的激活，表明该促炎信号通路受到抑制。此外，LPS诱导的IκBα降解不受急性饮酒的影响，这表明存在一种不依赖IκBα的机制，正如早期体外急性酒精研究中所观察到的那样。相比之下，急性饮酒会增加抗炎细胞因子IL-10的单核细胞产生。
我们的研究结果表明，急性饮酒具有双重抗炎作用，包括增强IL-10以及通过抑制NF-κB减弱单核细胞炎症反应。这些机制可能有助于适度饮酒对动脉粥样硬化的有益作用。
