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Ethanol Feeding Impairs Innate Immunity and Alters the Expression of Th1‐ and Th2‐Phenotype Cytokines in Murine Klebsiella Pneumonia
Author(s) -
Zisman David A.,
Strieter Robert M.,
Kunkel Steven L.,
Tsai Wan C.,
Wilkowski Jodi M.,
Bucknell Kathy A.,
Standiford Theodore J.
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb04303.x
Subject(s) - bronchoalveolar lavage , immunology , cytokine , pneumonia , klebsiella pneumoniae , lung , immunity , biology , klebsiella pneumonia , ingestion , medicine , immune system , endocrinology , biochemistry , escherichia coli , gene
The prolonged and excessive consumption of alcohol has been shown to predispose the host to a variety of infectious complications, which may be due, in part, to the inability to produce important activating cytokines. In this study, we assessed the effect of chronic alcohol ingestion on bacterial clearance, survival, and cytokine mRNA and protein expression in mice with Klebsiella pneumonia. Two‐week ethanol feeding resulted in substantial impairment in the clearance of K. pneumoniae and decreased survival, compared with CD‐1 mice receiving an isocaloric diet without ethanol. No differences were noted between control and ethanol groups in the total numbers or percent of bronchoalveolar lavage fluid neutrophils or macrophages at 24 and 48 hr post‐intratracheal K. pneumoniae. Importantly, the lungs of alcohol‐fed mice with Klebsiella pneumonia displayed a decrease or delay in the expression of interleukin (IL)‐12 p35 and p40 mRNA and interferon‐γ mRNA, respectively, as well as reduced IL‐12 and interferon‐γ protein levels, compared with controls. Conversely, a time‐dependent increase in lung IL‐10 mRNA and protein was noted in ethanol‐fed animals, compared with control animals challenged with K. pneumoniae. In summary, our studies indicate that ethanol ingestion results in a profound suppression of lung bacterial clearance and decreased survival in Klebsiella pneumonia, which occurs in association with a shift in the balance of lung cytokine mRNA and protein expression favoring Th2‐ rather than Th1‐phenotype cytokines.