Delta-9-tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of bacillus calmétte-guérin-activated macrophages

Burnette-Curley, Dana; Marciano‐Cabral, Francine; Fischer-Stenger, Krista; Cabral, Guy A.

doi:10.1016/0192-0561(93)90048-4

Cited by 39 publications

(15 citation statements)

References 30 publications

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“…THC and other cannabinoids have been shown to suppress macrophage functions such as phagocytosis, bactericidal activity, and spreading (Klein and Friedman 1990;Friedman et al 1991). In addition, THC has been shown to interfere with macrophage cell contact-dependent lysis of tumor cells, herpesvirus-infected cells, and amebae, and to deplete soluble tumoricidal activity elicited by macrophages exposed in vivo to the drug (Burnette-Curley et al 1993;Burnette-Curley and Cabral 1995). These observations are consistent with reports that THC inhibits the synthesis of proteins associated with primed and activated macrophages (Cabral and Mishkin 1989), alters cytokine secretion by activated macrophages (Watzl et al 1991;Nakano et al 1992), and inhibits cytokine gene expression by microglia (Puffenbarger et al 2000) (Fig.…”

Section: Modulation Of Antigen-presenting Cellssupporting

confidence: 83%

Cannabinoid-Induced Immune Suppression and Modulation of Antigen-Presenting Cells

Klein

Cabral

2006

Jrnl NeuroImmune Pharm

153

138

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The study of marijuana cannabinoid biology has led to many important discoveries in neuroscience and immunology. These studies have uncovered a new physiological system, the endocannabinoid system, which operates in the regulation of not only brain function but also the regulation of the immune system. Studies examining the effect of cannabinoid-based drugs on immunity have shown that many cellular and cytokine mechanisms are suppressed by these agents leading to the hypothesis that these drugs may be of value in the management of chronic inflammatory diseases. In this report, we review current information on cannabinoid ligand and receptor biology, mechanisms involved in immune suppression by cannabinoids with emphasis on antigen-presenting cells, and preclinical and clinical models analyzing the therapeutic potential of cannabinoid-based drugs.

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Section: Modulation Of Antigen-presenting Cellssupporting

confidence: 83%

Cannabinoid-Induced Immune Suppression and Modulation of Antigen-Presenting Cells

Klein

Cabral

2006

Jrnl NeuroImmune Pharm

153

138

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“…THC has been shown to overcome the restriction of the growth of Legionella pneumophila, a facultative intracellular bacterium that replicates readily in human and guinea pig macrophages and in peritoneal exudate macrophages from A/J mice (Arata et al 1991(Arata et al , 1992. THC also altered the capacity of macrophages in vitro to kill Naegleria fowleri (Burnette-Curley et al 1993), free-living amebae that cause a fatal disease in humans known as primary amoebic meningoencephalitis (PAME) (MarcianoCabral 1988).…”

Section: Marijuanamentioning

confidence: 97%

Drugs of Abuse, Immune Modulation, and AIDS

Cabral

2006

Jrnl Neuroimmune Pharm

112

100

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Illicit drugs such as amphetamines, cocaine, marijuana, and opiates alter immune function and decrease host resistance to microbes in vitro and in experimental animal models. Effects on the immune system may be mediated indirectly as a result of drug interactions in the central nervous system (CNS) or directly through activation of cognate receptors on various immune cell types. For marijuana and opioids, seven-transmembranal G protein-coupled receptors have been identified in the CNS and in the immune system that may play a functionally relevant role in immune modulation. There is accumulating evidence that sigma(1) receptors play a comparable role in cocaine-mediated alteration of immune responses. A mode by which these exogenously introduced substances affects immunity and host resistance may be by perturbing the balance of Th(1) proinflammatory versus Th(2) anti-inflammatory cytokines and lipid bioeffectors. However, while illicit drugs have been documented to alter immune functions in vitro and in animal models, there is a paucity of controlled longitudinal epidemiological studies that definitively correlate immunosuppressive effects with increased incidence of infections or immune disorders in humans, including infection with the human immunodeficiency virus (HIV) or disease progression to AIDS.

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“…Immune suppression is one of the major actions of cannabinoids, which are able to inhibit lymphocyte proliferation Schwarz et al, 1994], antibody production, natural killer cell activity [Specter et al, 1980], and macrophage activity [Tang et al, 1992;Burnette-Curley et al, 1993;Friedman et al, 1994]. Consistent with these inhibitory features, cannabinoids are known to diminish general resistance to bacterial or viral infection [Morahan et al, 1979;Klein et al, 1994;Newton et al, 1994], and to suppress host immune reactivity against tumor growth [Zhu et al, 2000].…”

mentioning

confidence: 88%

Effects of cannabinoids on LPS‐stimulated inflammatory mediator release from macrophages: Involvement of eicosanoids

Chang

Lee

Lin

2001

J of Cellular Biochemistry

204

126

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Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) is the major psychoactive component of marijuana and elicits pharmacological actions via cannabinoid receptors. Anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG) are endogenous ligands for cannabinoid receptors, which because of their structural similarities to arachidonic acid (AA), AEA, and 2-AG could serve as substrates for lipoxygenases and cyclooxygenases (COXs) that metabolize polyunsaturated fatty acids to potent bioactive molecules. In this study, we have compared the effects of Delta(9)-THC, AEA, 2-AG, and another cannabinoid agonist, indomethacin morpholinylamide (IMMA), on lipopolysaccharide (LPS)-induced NO, IL-6, and PGE(2) release from J774 macrophages. Delta(9)-THC, IMMA, and AEA diminish LPS-induced NO and IL-6 production in a concentration-dependent manner. 2-AG inhibits the production of IL-6 but slightly increases iNOS-dependent NO production. Delta(9)-THC and IMMA also inhibit LPS-induced PGE(2) production and COX-2 induction, while AEA and 2-AG have no effects. These discrepant results of 2-AG on iNOS and COX-2 induction might be due to its bioactive metabolites, AA and PGE(2), whose incubation cause the potentiation of both iNOS and COX-2 induction. On the contrary, the AEA metabolite, PGE(2)-ethanolamide, influences neither the LPS-induced NO nor IL-6 production. Taken together, direct cannabinoid receptor activation leads to anti-inflammatory action via inhibition of macrophage function. The endogenous cannabinoid, 2-AG, also serves as a substrate for COX-catalyzing PGE(2) production, which in turn modulates the action of CB2.

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Delta-9-tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of bacillus calmétte-guérin-activated macrophages

Cited by 39 publications

References 30 publications

Cannabinoid-Induced Immune Suppression and Modulation of Antigen-Presenting Cells

Cannabinoid-Induced Immune Suppression and Modulation of Antigen-Presenting Cells

Drugs of Abuse, Immune Modulation, and AIDS

Effects of cannabinoids on LPS‐stimulated inflammatory mediator release from macrophages: Involvement of eicosanoids

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