Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype

Abstract

Cannabinoids, the Cannabis constituents, are known to possess anti-inflammatory properties but the mechanisms involved are not understood. Here we show that the main psychoactive cannabinoid, Δ-9-tetrahydrocannabinol (THC), and the main nonpsychoactive cannabinoid, cannabidiol (CBD), markedly reduce the Th17 phenotype which is known to be increased in inflammatory autoimmune pathologies such as Multiple Sclerosis. We found that reactivation by MOG35-55 of MOG35-55-specific encephalitogenic T cells (cells that induce Experimental Autoimmune Encephalitis when injected to mice) in the presence of spleen derived antigen presenting cells led to a large increase in IL-17 production and secretion. In addition, we found that the cannabinoids CBD and THC dose-dependently (at 0.1-5 μM) suppressed the production and secretion of this cytokine. Moreover, the mRNA and protein of IL-6, a key factor in Th17 induction, were also decreased. Pretreatment with CBD also resulted in increased levels of the anti-inflammatory cytokine IL-10. Interestingly, CBD and THC did not affect the levels of TNFα and IFNγ. The downregulation of IL-17 secretion by these cannabinoids does not seem to involve the CB1, CB2, PPARγ, 5-HT1A or TRPV1 receptors. In conclusion, the results show a unique cannabinoid modulation of the autoimmune cytokine milieu combining suppression of the pathogenic IL-17 and IL-6 cytokines along with boosting the expression of the anti-inflammatory cytokine IL-10.

Histone Modifications Are Associated with Δ9-Tetrahydrocannabinol-mediated Alterations in Antigen-specific T Cell Responses

“…A recent study showed that THC reduces Th17 (49). However, in this study, these histone methylation markers were not associated with Rorc, which regulates Th17 (data not shown).…”

Immunoregulatory Role of Cannabinoids during Infectious Disease

“…In addition, serum levels of IFN-γ, IL-10, IL-12, or C-reactive protein in MS patients have not been reported to have any influence on the development of the disease [85]. Nevertheless, a study by Arevalo-Martin et al [86] The potential use of cannabinoids in the treatment of MS also involves the reduced synthesis and secretion of IL-17 by THC and CBD, thereby suppressing the Th17 response [87] which is commonly increased in patients with inflammatory autoimmune pathologies such as MS [88].…”

Cannabis and Exercise Science: A Commentary on Existing Studies and Suggestions for Future Directions

“…This raises questions about whether cannabis might be associated with behaviors that are linked to lower rates of obesity, such as physical activity. Some studies have suggested that cannabinoids may exert positive effects on health by decreasing inflammation and decreasing pain [5], and it is possible that such properties might have implications for recovery from exercise. There are also anecdotal reports that cannabis is used prior to athletic activity to enhance performance.…”