The acquired immunodeficiency syndrome (AIDS) is a disease affecting many organ systems, notably the immune, nervous and endocrine systems. Recent studies, by our laboratory and others, have suggested that a regulatory link may normally exist between these same three systems. In this project, our hypothesis to be tested is that the production of neuroendocrine hormones and/or responsiveness to these molecules by lymphocytes is altered by HIV infection and that this may mediate some of the endocrine and immune abnormalities seen in AIDS. To gain insight into both the pathophysiology of AIDS and the functioning of immune- neuroendocrine axis we propose to study the effects of HIV infection on hormone production and response in populations of lYmphoid cells at both cellular and molecular levels. The general aim is to determine if HIV and/or its products effect hormone production by primary and cultured lymphoid cells and if the same type of cells from HIV infected humans at various stages of disease are similarly dysfunctional. More specifically, cultured lymphoid cell lines of T, B, and macrophage lineage as well as primary peripheral blood lymphocytes (PBLs) will be treated with HIV or its subcomponents. Immunoassays will be used to measure basal and inducible production of corticotropin (ACTH), endorphin, enkephalins and thyroid stimulating hormone (TSH). Alterations by HIV of these hormones will be examined at the molecular level using oligonucleotide probes in Northern blot, in situ hybridization, or slot blot analyses. Also to be examined is the effect that HIV, or its components have on immune response modulation by neuroendocrine hormones. HIV treated cultured cell lines and PBLs will be analyzed in radioreceptor binding assays and by immunofluorescence to determine if hormone binding ability or receptor structure is altered. Functional assays such as interferon induction, mitogenesis, or adenylate cyclase activation will be assessed to determine if HIV or its components affect hormone modulation of these functions. Finally, lymphocytes from individuals at different stages of AIDS will be assessed for the abnormalities found in the in vitro studies. These studies should provide new insight into the role HIV infection of the immune system has on the endocrine abnormalities seen with AIDS and may suggest new therapies to either control the infection or treat the debilitating systemic alterations.
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