ETHANOL FEEDING IMPAIRS INNATE IMMUNITY AND ALTERS THE EXPRESSION OF TH1-PHENOTYPE AND TH2-PHENOTYPE CYTOKINES IN MURINE KLEBSIELLA-PNEUMONIA

The prolonged and excessive consumption of alcohol has been shown to p redispose the host to a variety of infectious complications, which may be due, in part, to the inability to produce important activating cyt okines. In this study, we assessed the effect of chronic alcohol inges tion on bacterial clearance, survival, and cytokine mRNA and protein e xpression in mice with Klebsiella pneumonia. Two-week ethanol feeding resulted in substantial impairment in the clearance of K. pneumoniae a nd decreased survival, compared with CD-1 mice receiving an isocaloric diet without ethanol, No differences were noted between control and e thanol groups in the total numbers or percent of bronchoalveolar lavag e fluid neutrophils or macrophages at 24 and 48 hr post-intratracheal K. pneumoniae, Importantly, the lungs of alcohol-fed mice with Klebsie lla pneumonia displayed a decrease or delay in the expression of inter leukin (IL)-12 p35 and p40 mRNA and interferon-gamma mRNA, respectivel y, as well as reduced IL-12 and interferon-gamma protein levels, compa red with controls. Conversely, a time-dependent increase in lung IL-10 mRNA and protein was noted in ethanol-fed animals, compared with cont rol animals challenged with K. pneumoniae, In summary, our studies ind icate that ethanol ingestion results in a profound suppression of lung bacterial clearance and decreased survival in Klebsiella pneumonia, w hich occurs in association with a shift in the balance of lung cytokin e mRNA and protein expression favoring Th2-rather than Th1-phenotype c ytokines.