The cannabinoid 2 receptor agonist [beta]-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration

Objective and design [beta]-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB2) receptor and exerts anti-inflammatory effects. In this study, we investigated the anti-inflammatory effect of BCP and another CB2 agonist, GP1a in inflammatory experimental model induced by Mycobacterium bovis (BCG). Methods C57Bl/6 mice were pretreated orally with BCP (0.5-50 mg/kg) or intraperitonealy with GP1a (10 mg/kg) 1 h before the induction of pleurisy or pulmonary inflammation by BCG. The direct action of CB2 agonists on neutrophils function was evaluated in vitro. Results [beta]-Caryophyllene (50 mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-[alpha] and CCL2/MCP-1. However, BCP inhibited CXCL1/KC, leukotriene B4 (LTB4), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10 µM) impaired chemotaxis toward LTB4 and adhesion to endothelial cells stimulated with TNF-[alpha], and both, BCP and GP1a, impaired LTB4-induced actin polymerization. Conclusion These results suggest that the CB2 receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.