Effect of alcohol consumption on host release of interleukin-17 during pulmonary infection with Klebsiella pneumoniae

Background: A link between alcohol abuse and bacterial pneumonia has been r ecognized for centuries, but mechanisms to explain this relationship are un clarified. Interleukin-17 (IL-17) is a lymphocyte-derived cytokine that is part of the inflammatory cytokine cascade. Previous studies from our labora tory indicated that IL-17 is released in lung tissue in a murine model of b acterial pneumonia caused by Klebsiella pneumoniae. The effects of alcohol consumption on pulmonary release of IL-17 are unknown. Methods: Mice were maintained on 20% ethanol in drinking water or on a cont rol diet without alcohol. After 2 weeks, alcohol and control mice were chal lenged with intratracheal K. pneumoniae. Mice were followed for survival af ter bacterial challenge, neutrophil recruitment was assayed as myeloperoxid ase, and IL-17 was measured in lung lavage fluid by enzyme-linked immunosor bent assay. In additional experiments, splenocytes from control mice were i ncubated with ethanol in vitro, and release of IL-17 was measured in cultur e supernatants. Finally, control and alcohol mice received intrapulmonary g ene transfer of E-1-deleted adenovirus containing the murine IL-17 gene. Th ese mice were then challenged with K, pneumoniae and followed for survival and neutrophil recruitment. Results: In these studies, we demonstrate that a 2-week history of ethanol consumption in mice suppresses release of IL-17 into lung tissue, decreases neutrophil recruitment, and increases mortality from experimental K. pneum onia. In vitro experiments confirm a direct suppressive effect of ethanol o n the release of IL-17 from splenocytes. In vivo administration of the IL-1 7 gene in an adenoviral vector to alcohol-consuming mice results in release of IL-17 into lavage fluid and normalizes neutrophil recruitment and morta lity after bacterial challenge. Conclusions: The results of these experiments strongly implicate IL-17 as a n important pathway for the immunosuppression associated with alcohol abuse and support gene therapeutic approaches to augment immune function in the alcoholic host or to treat infections associated with alcoholism.