PRECLINICAL STUDY: Differential effects of ethanol on IFN-γ- and TNF-α-producing splenic T lymphocytes in a murine model of gram-negative pneumonia

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Abstract

The incidence of bacterial pneumonia is increased in alcoholic patients. Alcohol consumption has been shown to impair cytokine production. Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) are critical for host defense against Klebsiella pneumoniae (K. pneumoniae). In order to examine the influence of alcohol on the immune response to infection, we investigated the frequency of TNF-α and IFN-γ produced by splenic T-lymphocytes in a murine model of gram-negative pneumonia initiated after 8 days of alcohol treatment. Thirty-two Balb/c mice were pretreated with ethanol (3 mg/g body weight) or saline intraperitoneally over 8 days. On day 7 half of each group was administered K. pneumoniae. Mice were sacrificed 24 hours later to excise lungs and liver for histological assessment and spleens for cell isolation. IFN-γ- and TNF-α-producing CD4+ and CD8+ lymphocytes were determined by FACS analysis. In mice with Klebsiella infection, the percentages of IFN-γ-producing CD4+ (P < 0.01) and CD8+ (P < 0.01) were significantly decreased, the percentages of TNF-α-producing CD4+ (P = 0.01) and CD8+ (P < 0.01) T cells were significantly elevated after alcohol treatment compared with mice with saline treatment. The histological assessment showed an aggravation of K. pneumoniae-induced pneumonia in alcohol-treated mice. Alcohol differentially affects IFN-γ and TNF-α production in Klebsiella-infected mice. Both effects obviously led to a weakened immune response as seen by increased histological damage. This suggests a role of T cells in the increased susceptibility of the alcoholic host to nosocomial infection due to inadequate cytokine response.

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