Acquired immune deficiency syndrome (AIDS) is a viral disease which causes progressive and irreversible immune suppression, associated with a marked depletion of CD4+ lymphocytes. During AIDS-related complex (ARC), an early stage of disease, chronic lymphadenopathy develops which is due in large part to polyclonal B cell activation i all lymphoid tissues. The relationship of lymphadenopathy to the latter immunosuppressive stages of disease is unclear; however, animal studies suggest that lymphadenopathy may represent a critical early event in the disease process. In this regard, marked similarities exist between ARC d certain autoimmune diseases, such as graft-versus-host disease and systemic lupus erythematosis. Prevention of lymphoproliferation has been associated with amelioration of autoimmune disease in these cases. Ethanol ingestion is known to inhibit both humoral and cellular immunity. Moreover, chronic alcohol abuse is common among drug users, a high risk group for AIDS. How ethanol-induced immunosuppression impinges on the development of AIDS is unknown. We propose to use a murine model of retroviral- induced AIDS to evaluate the effects of acute and chronic ethanol ingestion on the development of antiviral immunity and AIDS. In particular, we will determine the effects of ethanol on mortality i murine AIDS (MAIDS) and whether ethanol affects the induction of specific humoral and cellular antiviral immunity to the MAIDS virus. Finally, we will evaluate the effects of ethanol on the development of lymphadenopathy during MAID, with a focus on B cell hyperplasia nad polyclonal antibody production, activation and expansion of T cell subsets, autoimmune reactivity to self antigens and the production of cytokines, such as the interleukins, tumor necrosis factor and gamma interferon. These studies will contribute valuable information on the effects of alcohol abuse on the development and severity of AIDS and may suggest new possibilities where future studies could be focused in consideration of possible therapeutic intervention.
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