Fig. 6.

Cellular source and proposed targets of anti-inflammatory endocannabinoids in inflammatory bowel disease. a, cross-section of inflamed bowel with leukocyte infiltration [polymorphonuclear leukocytes (PNM), lymphocytes (Ly), macrophages, and mast cells]. b, in macrophages, LPS induces the production of TNF-α and chemokines (such as MIP-2macrophage inflammatory protein-2 and CXCL-8) as well as anandamide. Anandamide is released to act as an autocrine mediator to inhibit TNF-α and chemokine production via CB₁ or CB₂ receptors or both. Activation of CB₁ and CB₂ receptors may similarly inhibit TNF-α production in mast cells, with these effects resulting in decreased leukocyte infiltration and inflammation. Paracrine activation of CB₁ receptors on extrinsic and intrinsic enteric neurons inhibits acetylcholine (ACh) and tachykinin release, respectively, resulting in inhibition of gut motility. These effects are amplified by treatment with a FAAH inhibitor, which prevents the breakdown of anandamide. Reproduced with permission from Kunos and Pacher (2004) Nat Med 10:678–679. © Nature Publishing Group.