The overall goals of this proposal are to develop a center which will foster research concerning the role of ethanol on: (1) cellular immune function in animal models, (2) immunosuppression and development of acquired immunodeficiency diseases including retrovirus infection, and (3) mechanisms of liver toxicity via immunomodulation. Our approaches involve a multidisciplinary, basic science-oriented, research effort. It will develop an alcohol research center and include: 1) The relationships of alcohol use, retrovirus infection, immunomodulation and AIDS development to: - determine alcohol's effects on death rates - investigate in depth alcohol's actions on immune functions in mice with various levels of alcohol intake. - study in detail the immunological changes due to alcohol as a cofactor during retroviral infection on resistance to other pathogens. - determine ways to stimulate ethanol-suppressed host defenses and disease resistance during retroviral infection. 2) The use of well-defined animal model systems to: - determine interactions between alcohol use, nutritional stresses, immunoarchitecture changes and the resulting changes in resistance to murine retrovirus. - investigate the long-term effects of alcohol to modulate cellular immune functions as they correlate with enhancement of chemically- induced liver cancer in rats. - determine the role of toxin and alcohol-altered Kupffer cell functions in liver damage in rats. -study alcohol's effects on sinusoidal permeability, tissue oxygenation, cell migration in lymph. - measure and study host defense function of macrophages and Kupffer cells in vivo including in vivo microscopy as modified by ethanol and retroviral disease.
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