Alcohol abuse has many deleterious actions upon the host, but one of the more severe effects is immunosuppression and increased susceptibility to both systemic and pulmonary infections. The monocyte/macrophage, a critical cell in the inflammatory response, is thought to be a prime target of ethanol abuse resulting in derangements of its inflammatory effector functions. HIV/AIDS is also characterized by immunosuppression primarily due to a decrease in the number of CD4+ T-helper cell population. It has more recently been appreciated that HIV infection of CD4+ monocytes/macrophages alters their functional state and may compromise their responsiveness to opportunistic pathogens. Furthermore, alcohol abuse and HIV/AIDS often co-exist. It is important, therefore, to examine interactions between ethanol abuse and HIV disease progression, and the development of opportunistic infections. Using SIV- infected rhesus monkeys, a well-accepted model of HIV/AIDS, studies will test the following Specific Aims: 1) To determine the effect of in vitro ethanol exposure on the ability of alveolar macrophages and peripheral blood monocytes (isolated longitudinally during the progression of SIV infection) to initiate and regulate cytokine production in response to lipopolysaccharide (LPS), to undergo phagocytosis, and to generate an oxidative burst, 2) To characterize the effects f ethanol exposure in vitro on SIV infectivity of alveolar macrophages and peripheral blood monocytes from uninfected animals. These results will provide novel information necessary to further address interactions between ethanol, HIV disease progression, and resultant opportunistic infections.
