Effect of Alcohol Consumption on Host Release of Interleukin-17 During Pulmonary Infection With Klebsiella pneumoniae

Authors

  • Judd E. Shellito,

    Corresponding author
    1. Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Louisiana State University Health Sciences Center Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
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  • Min Quan Zheng,

    1. Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Louisiana State University Health Sciences Center Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
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  • Peng Ye,

    1. Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Louisiana State University Health Sciences Center Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
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  • Sanbao Ruan,

    1. Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Louisiana State University Health Sciences Center Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
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  • Mary K. Shean,

    1. Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Louisiana State University Health Sciences Center Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
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  • Jay Kolls

    1. Section of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Lung Biology and Immunotherapy, Louisiana State University Health Sciences Center Alcohol Research Center, and Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
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  • Supported by NIH Grants HL59724 (NHLBI) and AA08845 (NIAAA), by the Louisiana Health Excellence Fund, and by the LSUHSC Alcohol Research Center.

  • Presented in part at the annual meeting of the American Thoracic Society, May 2000, Toronto, Canada.

Reprint requests: Judd E. Shellito, MD, Section of Pulmonary and Critical Care Medicine, Louisiana Health Sciences Center, 1901 Perdido St., Ste. 3205, New Orleans, LA 70112; Fax: 504-568-4295; E-mail: jshell@lsuhsc.edu

Abstract

Background: A link between alcohol abuse and bacterial pneumonia has been recognized for centuries, but mechanisms to explain this relationship are unclarified. Interleukin-17 (IL-17) is a lymphocyte-derived cytokine that is part of the inflammatory cytokine cascade. Previous studies from our laboratory indicated that IL-17 is released in lung tissue in a murine model of bacterial 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 control diet without alcohol. After 2 weeks, alcohol and control mice were challenged with intratracheal K. pneumoniae. Mice were followed for survival after bacterial challenge, neutrophil recruitment was assayed as myeloperoxidase, and IL-17 was measured in lung lavage fluid by enzyme-linked immunosorbent assay. In additional experiments, splenocytes from control mice were incubated with ethanol in vitro, and release of IL-17 was measured in culture supernatants. Finally, control and alcohol mice received intrapulmonary gene transfer of E-1–deleted adenovirus containing the murine IL-17 gene. These 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. pneumonia. In vitro experiments confirm a direct suppressive effect of ethanol on the release of IL-17 from splenocytes. In vivo administration of the IL-17 gene in an adenoviral vector to alcohol-consuming mice results in release of IL-17 into lavage fluid and normalizes neutrophil recruitment and mortality after bacterial challenge.

Conclusions: The results of these experiments strongly implicate IL-17 as an 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.

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