The long-term objective of this project is to confirm in alcohol- consuming human subjects mechanisms of alcohol-induced immunosuppression identified in the research projects. Alcohol consumption is a well recognized risk factor for pulmonary infections in humans, although the mechanism(b) which alcohol interferes with host defense against infection have not been well clarified. It is our hypothesis that chronic alcohol ingestion interferes with selected functions of resident lung macrophages, alveolar macrophages, causing decreased host resistance to pulmonary infection. In the proposed studies, we will utilize fiberoptic bronchoscopy to recover alveolar macrophages from the lungs of control and alcoholic subjects. The recovered alveolar macrophages will then be assayed in vitro for the following host defense functions: Release of tumor necrosis factor Release of reactive nitrogen intermediates Release of granulocyte colony-stimulating factor These studies will be performed on anesthetized patients undergoing elective, nonpulmonary surgery and on selected outpatients with alcoholic cirrhosis. Outpatient bronchoscopy and initial preparation of the lavaged cells will take place in goal of these studies will be to characterize mechanisms by which alcohol consumption interferes with specific functions of alveolar macrophages important in the killing of microorganisms and in the recruitment of inflammatory cells into the lungs. All studies will be controlled for the subject smoking status. Special attention will be paid to the role of cirrhosis as a separate immunosuppressive factor in addition to alcohol consumption.
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