Cannabinoids decrease the Th17 inflammatory autoimmune phenotype

Ewa Kozela*, Ana Juknat, Nathali Kaushansky, Neta Rimmerman, Avraham Ben-Nun, Zvi Vogel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

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, -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.

Original languageAmerican English
Pages (from-to)1265-1276
Number of pages12
JournalJournal of NeuroImmune Pharmacology
Volume8
Issue number5
DOIs
StatePublished - Dec 2013
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments This work was supported by the Dr Miriam and Sheldon G. Adelson Medical Research Foundation. A.J. is supported by the Israeli Ministry for Absorption in Science.

Keywords

  • Cannabinoid
  • EAE
  • Encephalitogenic T cells
  • IL-10
  • IL-17
  • IL-6

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