Ethanol has been shown to have a profound effect on the immune system of rodents and human beings. Another important aspect of host defense mechanisms that is likely to be affected by ethanol is the mucosal immune system to include the gastrointestinal immune system. The present proposal is designed to test the hypothesis that ethanol ingestion in a liquid diet alters the function, numbers, or both of the effector cells involved in the gastrointestinal immune system. This will be accomplished by isolating lymphoid cells from the mesenteric lymph nodes, Pyer's patches, and the intraepithelial lymphocytes and macrophages and assessing the numbers and phenotypes of these cells by flow cytometric methods. The functional activity of cells will also be assessed by stimulation with monoclonal antibodies to the alpha/beta T-cell receptor molecules or the gamma/delta T-cell receptor molecules. Macrophage function will be assessed following stimulation with interferon or lipopolysaccharide by measuring nitric oxide synthesis, tumor necrosis factor, and interleukin-1 production. The effects of ethanol exposure will also be measured with the use of in vivo assays including susceptibility to Salmonella typhimurium, histologic evidence of pathology and changes in permeability, and macrophage activation in response to systemic challenges with lipopolysaccharide. With the use of molecular biologic techniques the effect of ethanol on the induction of macrophage-associated cytokines (interleukin-1, tumor necrosis factor interleukin-6) and nitric oxide synthase following lipopolysaccharide administration will be assessed with the use of polymerase chain reaction techniques.
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