Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells

Acta Physiol (Oxf). 2015 May;214(1):63-74. doi: 10.1111/apha.12474. Epub 2015 Mar 10.


Aims: To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro-inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS). CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown.

Methods: Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2.

Results: Pro-inflammatory cytokines IL-1β, IL-6 and TNF-α (the latter likely NF-κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL-1β, IL-6 and TNF-α mRNA in blood of patients with MS compared with controls.

Conclusion: The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.

Keywords: cannabinoid receptor 1; cannabinoid receptor 2; inflammatory cytokines; multiple sclerosis; regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Interleukin-1beta / pharmacology*
  • Interleukin-6 / pharmacology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism*
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Young Adult


  • Interleukin-1beta
  • Interleukin-6
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Tumor Necrosis Factor-alpha