The public health risk of marijuana smoking in adults and juveniles is not clear and further studies are indicated. Smoking marijuana can alter lymphocyte function and injection of cannabinoid substances into animals can modify the biological responsiveness of lymphocytes and macrophages. We have shown that animals injected with cannabinoids become deficient in IFN production, IL-1 production, NK cell activity and CTL function. Furthermore, the addition of THC or 11-OH-THC in vitro can affect antibody formation by lymphocytes, either enhance or suppress proliferation in response to T and B cell mitogens, uniquely affect lymphocytes from various lymphoid organs, modulate IL-2 and IFN production, suppress the killing ability of CTLs and NK cells, suppress macrophage spreading and phagocytosis, and either enhance or suppress the production of IL-1. Our results also suggest that lymphocyte function in juvenile animals is more greatly affected by THC than that of adult animals. It has been reported that marijuana can modify host resistance to infectious agents, however, the cellular basis for this attenuation is not known. We feel that our results and the results of others suggest that marijuana components reversibly modulate leukocyte function possibly by mechanisms involving membrane phospholipid/protein kinase C/arachidonic acid pathways, and that exposure of animals to marijuana can modify host resistance to infectious agents. Accordingly, we propose to examine the marijuana influence at the whole animal level and at the cellular. We will test host resistance to an opportunistic facultative intracellular bacteria (Legionella pneumophila) by animal i.v. injection with select cannabinoids followed by a challenge infection and analysis of survival rates and organ CFU dissimination. The cellular basis for the cannabinoid induced modification of host resistance will be examined in studies measuring antibody, TNF and IFN production, and macrophage bactericidal capacity. We will test the effect of select cannabinoids on freshly isolated and cloned T lymphocytes, NK cells, and macrophages. Studies will include cannabinoid effects on T cell proliferation, IL-2 production and NK cell killing, along with macrophage phagyotosis and IL-1 production. At the molecular level we will examine effects on cellular protein phosphorylation, cytoplasmic calcium concentration, membrane phospholipid metabolism, and arachidonic acid and leukotriene production. These studies will further our understanding of the marijuana influence at both the whole animal and molecular levels and also contribute to a better understanding of the cell biology of the immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003646-07
Application #
3208201
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1984-03-01
Project End
1991-09-29
Budget Start
1990-09-01
Budget End
1991-09-29
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of South Florida
Department
Type
Schools of Medicine
DUNS #
City
Tampa
State
FL
Country
United States
Zip Code
33612
Newton, Catherine A; Chou, Ping-Jen; Perkins, Izabella et al. (2009) CB(1) and CB(2) cannabinoid receptors mediate different aspects of delta-9-tetrahydrocannabinol (THC)-induced T helper cell shift following immune activation by Legionella pneumophila infection. J Neuroimmune Pharmacol 4:92-102
Newton, Cathy A; Perkins, Izabella; Widen, Raymond H et al. (2007) Role of Toll-like receptor 9 in Legionella pneumophila-induced interleukin-12 p40 production in bone marrow-derived dendritic cells and macrophages from permissive and nonpermissive mice. Infect Immun 75:146-51
Klein, Thomas W; Cabral, Guy A (2006) Cannabinoid-induced immune suppression and modulation of antigen-presenting cells. J Neuroimmune Pharmacol 1:50-64
Lu, Tangying; Newton, Cathy; Perkins, Izabella et al. (2006) Cannabinoid treatment suppresses the T-helper cell-polarizing function of mouse dendritic cells stimulated with Legionella pneumophila infection. J Pharmacol Exp Ther 319:269-76
Lu, Tangying; Newton, Cathy; Perkins, Izabella et al. (2006) Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL-12p40 in mouse bone marrow-derived dendritic cells infected with Legionella pneumophila. Eur J Pharmacol 532:170-7
Klein, Thomas W; Newton, Cathy; Larsen, Kellie et al. (2004) Cannabinoid receptors and T helper cells. J Neuroimmunol 147:91-4
Newton, Catherine A; Lu, Tangying; Nazian, Stanley J et al. (2004) The THC-induced suppression of Th1 polarization in response to Legionella pneumophila infection is not mediated by increases in corticosterone and PGE2. J Leukoc Biol 76:854-61
Klein, Thomas W; Newton, Cathy; Larsen, Kellie et al. (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74:486-96
Friedman, Herman; Newton, Catherine; Klein, Thomas W (2003) Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev 16:209-19
Nong, L; Newton, C; Friedman, H et al. (2001) CB1 and CB2 receptor mRNA expression in human peripheral blood mononuclear cells (PBMC) from various donor types. Adv Exp Med Biol 493:229-33

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