author's abstract.) AIDS is a disease affecting many organs; notably, those of the immune, nervous, and neuroendocrine systems. The overall hypothesis in this application 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. Previously, these investigators found that the AIDS virus, HIV, induces the neuroendocrine hormone, adrenocorticotrophin (ACTH), in lymphocytes. Further, they found structural and functional similarity between CRF and the major envelope protein of HIV, gp120. Apparently, therefore, this structural similarity reflects function. In the research proposed, the investigators will characterize this homology in structural and functional terms in order to determine the ability and likelihood that HIV's lymphoid and non-lymphoid effects are through CRF receptors. The effects of HIV infection on hormone production and response in populations of neuroendocrine and lymphoid cells will be studied at both the cellular and molecular levels. 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 either to control the infection or to 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 #
2R01DK041034-04
Application #
3241601
Study Section
AIDS and Related Research Study Section 7 (ARRG)
Project Start
1989-02-01
Project End
1995-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
4
Fiscal Year
1992
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
Smith, E M; Cadet, P; Stefano, G B et al. (1999) IL-10 as a mediator in the HPA axis and brain. J Neuroimmunol 100:140-8
Hashemi, F B; Hughes, T K; Smith, E M (1998) Human immunodeficiency virus induction of corticotropin in lymphoid cells. J Clin Endocrinol Metab 83:4373-81
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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