Lymphocytes cannabinoids

Keywords B lymphocytes Cannabinoid receptors Cannabinoids Cytokines Endocannahinoids Human immunodeficiency virus Immunity Infections Macrophages Mast cells Microglia Natural killer cells THC Therapeutics T lymphocytes... 

Peterson PK, Gekker G, Hu S, Cabral G, Lokensgard JR (2004) Cannabinoids and morphine differentially affect HIV-1 expression in CD4(-t) lymphocyte and microglial ceU cultures. J Neuroimmunol 147(1-2) 123-126... 

This drug has marked immunomodulatory effects and can alter the normal function of T and B lymphocytes, NK cells and macrophages, both in vivo and in vitro, in humans and animals (Table 30.1).910 Although the molecular and cellular mechanisms for these effects are not fully defined, it is believed that both receptor and non-receptor mechanisms are involved. Cannabinoid receptors (CBRs) are G-protein coupled 7-... 

In vivo studies showed that in vitro proliferation of lymphocytes isolated from marijuana smokers is suppressed, especially with heavy marijuana smoking, and that the relative proportion of lymphocyte subpopulations was also altered. Concentrations of serum IgG are decreased and IgE concentrations are increased in marijuana smokers. Furthermore, phagocytic and bactericidal activity of alveolar macrophages from heavy marijuana smokers are decreased. These effects translate into reduced host resistance following administration of cannabinoids, including THC, in both humans and animals (Table 30.2). Increased susceptibility has been demonstrated to opportunistic microbes including HIV, Herpes simplex virus, Friend leukemia virus Listeria, Treponema pallidum, and Legionella. 

The presence of cannabinoid receptors in the immune system has led to consideration of the effects of cannabis on its function. Cannabinoid receptors have been found in spleen cells (Kaminski et al. 1992). Activation of these receptors would inhibit their function in the immune response. Similar suppressant effects occur on lymphocytes (Diaz et al. 1993). THC and anandamide inhibit macrophage-mediated tumor necrosis (Cabral et al. 1995). Despite these effects, their functional significance remains to be determined. These effects are most likely subtle. 

Tetrahydrocannabinol depresses lymphocyte and macrophage activity in cell cultures, while in rats in vivo it directly suppresses natural killer cell activity and impairs T lymphocyte transformation by phytohemagglutinin in concentrations of cannabinoids achievable with the usual doses (119). Variable results have been obtained in man in tests of circulating T cells and hormonal immunity (120). 

Delta-9-THC is the main active constituent extracted from Cannabis sativa (Tuner, 1985 in Marijuana 1984, Ed. Harvey, DY, IRL Press, Oxford). Numerous articles have described not only psychotropic effects of cannabinoids but also their influence on the immune function [Hollister L. E., J. Psychoact. Drugs 24 (1992) 159-164]. The majority of in vitro studies have shown that cannabinoids have immunosuppressant effects inhibition of the mitogen induced proliferative responses of T lymphocytes and B lymphocytes [Luo, Y. D. et ah, Int. J. Immuno-pharmacol. (1992) 14,49-56 Schwartz, H. et at., J. Neuroimmunol. (1994) 55,107-115], inhibition of the activity of cytotoxic T cells [Klein et at., J. Toxicol. Environ. Health (1991) 32, 465-477], inhibition of the microbicidal activity of macrophages and of TNF-a synthesis [Arata, S. et at.. Life Sci. (1991) 49, 473-479 Fisher-Stenger et al., J. Pharm. Exp. Then (1993) 267, 1558-1565] and inhibition of the cytolytic activity and the TNFa production of large granular lymphoc3rtes [Kusher et al.. Cell. Immun. (1994) 154, 99-108],... 

B lymphocytes have been reported to express relatively high levels of the CB2 receptor (Carayon et al. 1998 Galiegue et al. 1995 Lynn and Herkenham 1994). Thus, it is not surprising that cannabinoid agonists should exert major effects on their functional activities. Klein et al. (1985) noted that addition of THC to mouse splenocyte cultures suppressed not only T lymphocyte proliferation in response to the mitogens ConA and PHA, but also that of B lymphocytes induced by LPS, a B cell mitogen. The hydroxylated metabolite of THC, 11 -hydroxy-THC, was observed to be much less potent in this inhibition. 

Luo YD, Patel MK, Wiederhold MD, Ou DW (1992) Effects of cannabinoids and cocaine on the mitogen-induced transformations of lymphocytes of human and mouse origins. Int J Immunopharmacol 14 49-56... 

Nahas GG, Morishima A, Desoize B (1977) Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Fed Proc 36 1748-1752... 

Many in vitro and in vivo studies have shown that cannabinoids are immunosuppressive agents (Roth et al, 2002 Klein et al. 2003). In this context, cannabinoids induce apoptosis of human peripheral blood mononuclear cells (Schwarz et al. 1994) as well as of mouse macrophages and lymphocytes (Zhu et al. 1998). THC also inhibits the proliferation and induces apoptosis of mouse thymocytes and splenocytes in culture and in mice (McKallip et al. 2002b). Moreover, various... 

Schwarz H, Blanco FJ, Lotz M (1994) Anadamide, an endogenous cannabinoid receptor agonist inhibits lymphocyte proliferation and induces apoptosis. J Neuroimmunol 55 107-115... 

Key Words Cannabinoids immune function splenocytes T cells lymphocyte proliferation macrophages c5dokines mitogen-activated kinase CB2R knockout mouse. 

The immunomodulatory properties of A -THC [48] are likely due to the interaction with CB2 receptors, highly expressed in cells of the immune system (T-cells, B-cells, macrophages). The effect on the immune system of cannabinoid administration appears to be hormesic, and related to the dosage. Indeed, high doses of caimabinoids suppress immune responses, while more physiologically relevant concentrations of cannabinoids result in metabolic stimulation of lymphocytes and in an increase in pro-inflammatory cytokine production rather than immunosuppression. It has been proposed that the immunosuppressive properties of cannabinoids can find application in the treatment of multiple sclerosis. 

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