Effects of pro‐inflammatory cytokines on cannabinoid CB (1) and CB (2) receptors in immune cells

AIMS: To investigate the regulation of cannabinoid receptors CB (1) and CB (2) on immune cells by pro‐inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS). CB (1) and CB (2) signalling may be anti‐inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB (1) and CB (2) expression and function are unknown. METHODS: Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB (1) and CB (2) 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 CB (1) and CB (2) protein was determined by flow cytometry. CB (1) and CB (2) 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 CB (1) and CB (2) on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB (1) and CB (2) and increased IL‐1β, IL‐6 and TNF‐α mRNA in blood of patients with MS compared with controls. CONCLUSION: The levels of CB (1) and CB (2) can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.