Elsevier

Mucosal Immunology

Volume 4, Issue 5, September 2011, Pages 574-583
Mucosal Immunology

Article
The endogenous cannabinoid system in the gut of patients with inflammatory bowel disease

https://doi.org/10.1038/mi.2011.18Get rights and content
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Abstract

Activation of cannabinoid receptors (CBs) by endocannabinoids impacts on a number of gastrointestinal functions. Recent data indicate that CB1 agonists improve 2,4-dinitrobenzene sulfonic acid-induced colitis in mice, thus suggesting a role for the endocannabinoid agonist anandamide (AEA) in protecting the gut against inflammation. We here examined the gut endocannabinoid system in inflammatory bowel disease (IBD) patients, and investigated the ex vivo and in vitro effects of the non-hydrolysable AEA analog methanandamide (MAEA) on the mucosal proinflammatory response. The content of AEA, but not of 2-arachidonoyl-glycerol and N-palmitoylethanolamine, was significantly lower in inflamed than uninflamed IBD mucosa, and this was paralleled by lower activity of the AEA-synthesizing enzyme N-acyl-phosphatidylethanolamine-specific phospholipase D and higher activity of the AEA-degrading enzyme fatty acid amide hydrolase. MAEA significantly downregulated interferon-γ and tumor necrosis factor-α secretion by both organ culture biopsies and lamina propria mononuclear cells. Although these results are promising, further studies are needed to determine the role of cannabinoid pathways in gut inflammation.

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Published online: 6 4 2011

Supplementary information The online version of this article (doi:10.1038/mi.2011.18) contains supplementary material, which is available to authorized users.

An erratum to this article is available online at https://doi.org/10.1038/mi.2011.23.