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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK041034-01
Application #
3241600
Study Section
Diabetes and Digestive and Kidney Diseases Special Grants Review Committee (DDK)
Project Start
1989-02-01
Project End
1992-01-31
Budget Start
1989-02-01
Budget End
1990-01-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
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Smith, E M (1997) Hormonal activities of cytokines. Chem Immunol 69:185-202
Stefano, G B; Smith, E M (1996) Adrenocorticotropin--a central trigger in immune responsiveness: tonal inhibition of immune activation. Med Hypotheses 46:471-8
Opp, M R; Rady, P L; Hughes Jr, T K et al. (1996) Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats [published errata appear in Am J Physiol 1996 Aug;271(2 Pt 2):section R following table of contents and 1996 Dec;271(6 Pt 3):section R follow Am J Physiol 270:R963-70
Rady, P L; Smith, E M; Cadet, P et al. (1995) Presence of interleukin-10 transcripts in human pituitary and hypothalamus. Cell Mol Neurobiol 15:289-96
Opp, M R; Smith, E M; Hughes Jr, T K (1995) Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. J Neuroimmunol 60:165-8
Hughes, T K; Fulep, E (1995) Effects of retinoic acid (vitamin A) on tumor necrosis factor cytolytic action. Biochem Biophys Res Commun 206:223-9
Hughes, T K; Cadet, P; Rady, P L et al. (1994) Evidence for the production and action of interleukin-10 in pituitary cells. Cell Mol Neurobiol 14:59-69
Stefano, G B; Smith, E M; Cadet, P et al. (1993) HIV gp120 alteration of DAMA and IL-1 alpha induced chemotaxic responses in human and invertebrate immunocytes. J Neuroimmunol 43:177-84

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