title: Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.
abstract: BACKGROUND
  ∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors.
  
  
  METHODS
  We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro.
  
  
  RESULTS
  Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner.
  
  
  CONCLUSIONS
  Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.
authors.affiliation: Laboratory of Experimental Dermatology, Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Gaffal
authors.forename: M
authors.initials: M
authors.lastname: Cron
authors.forename: N
authors.initials: N
authors.lastname: Glodde
authors.forename: T
authors.initials: T
authors.lastname: Tüting
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D004139:Dinitrofluorobenzene / Q000633:toxicity*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000008:administration & dosage* / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061251:Primary Cell Culture; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D013759:Dronabinol; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene
keywords: T cells; cannabinoids; contact allergy; inflammation; keratinocytes