Girouard L, Mandrekar P, Catalano D, Szabo G
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
Alcohol Clin Exp Res. 1998 Feb;22(1):211-6.
Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, suggesting that ethanol can induce a dysbalance of monocyte-derived mediator production at the expense of Th1 cytokines. However, we found that monocyte activation with interferon-gamma (IFN-gamma) can prevent the preferential IL-10 induction by ethanol. IFN-gamma (100 units/ml) inhibited monocyte IL-10 production whether induced by 1 microg/ml of lipopolysaccharide (p < 0.01), 1 microg/ml of SEB (p < 0.02), or a combination of bacterial stimulation + ethanol (lipopolysaccharide: p < 0.01). Furthermore, decreased IL-10 was concomitant to an increase in IL-12 production in IFN-gamma-treated monocytes. Moreover, acute ethanol treatment augmented IL-12 production in IFN-gamma-treated monocytes in response to SEB stimulation (25 mM ethanol, p < 0.01; 100 mM ethanol, p < 0.01). Experiments with anti-IL-10 neutralizing antibody show that ethanol may prevent monocyte IL-12 induction via IL-10. These results suggest that inhibition of ethanol-induced IL-10 production by IFN-gamma treatment is permissive for IL-12 induction by alcohol stimulation in monocytes. Thus, our results imply that the presence or absence of IFN-gamma is critical in determining the effect of acute ethanol treatment on monocyte IL-12 versus IL-10 induction.
急性乙醇处理会导致人单核细胞的抗原呈递能力下降（Th1型免疫）以及白细胞介素IL-10（Th2细胞因子）产生增加。单核细胞可分别通过产生IL-12和IL-10对Th1（IL-12）和Th2（IL-10）免疫反应产生影响。因此，我们检验了这样一个假设，即急性酒精处理可能通过改变单核细胞IL-12和IL-10的产生来影响Th1/Th2免疫平衡。单独的急性乙醇处理（25至100 mM）及其与细菌刺激物金黄色葡萄球菌肠毒素B（SEB）联合处理均未诱导分离的血液单核细胞产生IL-12。相反，相同的生理酒精浓度会增加单核细胞IL-10水平，这表明乙醇可诱导单核细胞衍生介质产生失衡，以Th1细胞因子为代价。然而，我们发现用干扰素-γ（IFN-γ）激活单核细胞可防止乙醇优先诱导IL-10。IFN-γ（100单位/毫升）抑制单核细胞IL-10的产生，无论其是由1微克/毫升脂多糖诱导（p<0.01）、1微克/毫升SEB诱导（p<0.02），还是由细菌刺激+乙醇联合诱导（脂多糖：p<0.01）。此外，在IFN-γ处理的单核细胞中，IL-10减少伴随着IL-12产生增加。此外，急性乙醇处理增强了IFN-γ处理的单核细胞对SEB刺激的IL-12产生（25 mM乙醇，p<0.01；100 mM乙醇，p<0.01）。用抗IL-10中和抗体进行的实验表明，乙醇可能通过IL-10阻止单核细胞IL-12的诱导。这些结果表明，IFN-γ处理抑制乙醇诱导的IL-10产生有利于酒精刺激单核细胞诱导IL-12。因此，我们的结果表明，IFN-γ的存在与否对于确定急性乙醇处理对单核细胞IL-12与IL-10诱导的影响至关重要。
