The long term objectives of this proposal are to gain an understanding of the mechanism(s) of the immunosuppressive activity of the marijuana component delta-9-tetrahydrocannabinol (THC).
The specific aims are to determine the cellular and molecular mechanisms by which THC inhibits the natural killer (NK) cell, lymphocyte blastogenesis and macrophage phagocytic activities of human peripheral blood leukocytes, although the study will initially focus on NK cell cytotoxicity. By doing so, an understanding of ways in which this type of immune suppression can be reversed by intervention with immunostimulatory substances, such as interleukin 2 can be acquired. Also, with regard to the immunosuppressive activity of THC these studies are intended to determine if marijuana might contribute to the onset of overt AIDS in individuals infected by the human immunodeficiency virus (HIV). These goals will be reached by studying the importance of cytokines (or their absence) in the mediation of THC induced suppression, examining the function of metabolic pathways known to be involved in lymphocyte and macrophage activation, and examining whether leukocytes from HIV infected individuals are more severely depressed in immune reactivity and produce greater numbers of infectious HIV. Ultimately, the goal is to overcome all of the detrimental effects of THC using immunomodulatory substances.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004141-06
Application #
2117028
Study Section
Sociobehavioral Subcommittee (DAAR)
Project Start
1987-05-01
Project End
1993-10-30
Budget Start
1992-05-15
Budget End
1993-10-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of South Florida
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612
Ongradi, J; Specter, S; Horvath, A et al. (1999) [Additive effect of marihuana and retrovirus in the anergy of natural killer cells in mice] Orv Hetil 140:81-4
Ongradi, J; Specter, S; Horvath, A et al. (1998) Combined in vitro effect of marijuana and retrovirus on the activity of mouse natural killer cells. Pathol Oncol Res 4:191-9
Zheng, Z M; Specter, S C (1996) Delta-9-tetrahydrocannabinol suppresses tumor necrosis factor alpha maturation and secretion but not its transcription in mouse macrophages. Int J Immunopharmacol 18:53-68
Zheng, Z M; Specter, S (1996) Dynamic production of tumour necrosis factor-alpha (TNF-alpha) messenger RNA, intracellular and extracellular TNF-alpha by murine macrophages and possible association with protein tyrosine phosphorylation of STAT1 alpha and ERK2 as an early signal. Immunology 87:544-50
Zheng, Z M; Specter, S (1996) Delta-9-tetrahydrocannabinol: an inhibitor of STAT1 alpha protein tyrosine phosphorylation. Biochem Pharmacol 51:967-73
Zheng, Z M; Specter, S C; Lancz, G (1995) Bovine serum albumin preparations enhance in vitro production of tumor necrosis factor alpha by murine macrophages. Immunol Invest 24:737-56
Zheng, Z M; Specter, S (1994) Suppression by delta-9-tetrahydrocannabinol of lipopolysaccharide-induced and intrinsic tyrosine phosphorylation and protein expression in mouse peritoneal macrophages. Biochem Pharmacol 47:2243-52
Diaz, S; Specter, S; Vanderhoek, J Y et al. (1994) The effect of delta-9-tetrahydrocannabinol on arachidonic acid metabolism in human peripheral blood mononuclear cells. J Pharmacol Exp Ther 268:1289-96
Trisler, K; Specter, S (1994) Delta-9-tetrahydrocannabinol treatment results in a suppression of interleukin-2-induced cellular activities in human and murine lymphocytes. Int J Immunopharmacol 16:593-603
Diaz, S; Specter, S; Coffey, R G (1993) Suppression of lymphocyte adenosine 3':5'-cyclic monophosphate (cAMP) by delta-9-tetrahydrocannabinol. Int J Immunopharmacol 15:523-32

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