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

Abstract

Objective and design: β-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: β-Caryophyllene (50 mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-α 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-α, 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.

Keywords: CB2 receptor; Chemotaxis; GP1a; Mycobacteria; Neutrophil.