A CB2 Receptor Agonist Reduces the Production of Inflammatory Mediators and Improves Locomotor Activity in Experimental Autoimmune Encephalomyelitis

Abstract

Background: Cannabinoids (CBs) have been found to regulate the immune system, affect innate and adaptive immune responses, and reduce inflammatory reactions. This study assessed the therapeutic effects of GW-405833 synthetic CB2 agonist on inflammatory factors as well as locomotor activity in experimental autoimmune encephalomyelitis (EAE). Methods: In this experimental study, 48 adult male C57BL/6 mice were randomly and equally assigned to eight groups. By injecting 250 mg of MOG35-55 peptide, EAE was induced. Every other day for 17 days after EAE onset, EAE-afflicted mice in groups 1-3 received an intraperitoneal injection of GW-405833 at a dose of 3, 10, and 30 mg/kg, respectively. Clinical status and locomotor activity, measured using the beam walking assay, were assessed every other day during the first 17 days after EAE onset. Mice were euthanized in day 17th of treatment and the serum levels of the IL-1 beta, IL-12, CRP, and TNF-alpha proinflammatory cytokines as well as IL-4 and TGF-beta anti-inflammatory cytokines were measured by ELISA method. Results: Clinical manifestations of EAE in groups 2 and 3 were significantly milder than group 4 and locomotor activity in groups 1-3 was significantly better than group 4 in days 5-17 (p< 0.05). GW-405833 also significantly decreased the levels of IL-12, TNF-alpha, and CRP and significantly increased the levels of IL-4 and TGF-beta but had no significant effects on the level of IL-1 beta. GW-405833 was not associated with significant side effects. Conclusions: The CB2 receptor agonist GW-405833, improves clinical conditions and reduces inflammation in mice with EAE.