Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors

Allergy. 2013 Aug;68(8):994-1000. doi: 10.1111/all.12183. Epub 2013 Jul 29.

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.

Keywords: T cells; cannabinoids; contact allergy; inflammation; keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Dermatitis, Allergic Contact / genetics
  • Dermatitis, Allergic Contact / pathology*
  • Dermatitis, Allergic Contact / prevention & control*
  • Dinitrofluorobenzene / toxicity*
  • Disease Models, Animal
  • Dronabinol / administration & dosage*
  • Dronabinol / pharmacology
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / biosynthesis
  • Keratinocytes / drug effects
  • Keratinocytes / immunology
  • Keratinocytes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Primary Cell Culture
  • Receptor, Cannabinoid, CB1* / deficiency
  • Receptor, Cannabinoid, CB1* / genetics
  • Receptor, Cannabinoid, CB1* / physiology
  • Receptor, Cannabinoid, CB2* / deficiency
  • Receptor, Cannabinoid, CB2* / genetics
  • Receptor, Cannabinoid, CB2* / physiology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Dronabinol
  • Interferon-gamma
  • Dinitrofluorobenzene