A CB۲ Receptor Agonist Reduces the Production of Inflammatory Mediators and Improves Locomotor Activity in Experimental Autoimmune Encephalomyelitis

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-۴۰۵۸۳۳ synthetic CB۲ agonist on inflammatory factors as well as locomotor activity in experimental autoimmune encephalomyelitis (EAE). Methods: In this experimental study, ۴۸ adult male C۵۷BL/۶ mice were randomly and equally assigned to eight groups. By injecting ۲۵۰ mg of MOG۳۵-۵۵ peptide, EAE was induced. Every other day for ۱۷ days after EAE onset, EAE-afflicted mice in groups ۱–۳ received an intraperitoneal injection of GW-۴۰۵۸۳۳ at a dose of ۳, ۱۰, and ۳۰ mg/kg, respectively. Clinical status and locomotor activity, measured using the beam walking assay, were assessed every other day during the first ۱۷ days after EAE onset. Mice were euthanized in day ۱۷th of treatment and the serum levels of the IL-۱ß, IL-۱۲, CRP, and TNF-α proinflammatory cytokines as well as IL-۴ and TGF-ß anti-inflammatory cytokines were measured by ELISA method. Results: Clinical manifestations of EAE in groups ۲ and ۳ were significantly milder than group ۴ and locomotor activity in groups ۱–۳ was significantly better than group ۴ in days ۵–۱۷ (p< ۰.۰۵). GW-۴۰۵۸۳۳ also significantly decreased the levels of IL-۱۲, TNF-α, and CRP and significantly increased the levels of IL-۴ and TGF-ß but had no significant effects on the level of IL-۱ß. GW-۴۰۵۸۳۳ was not associated with significant side effects. Conclusions: The CB۲ receptor agonist GW-۴۰۵۸۳۳, improves clinical conditions and reduces inflammation in mice with EAE.

کلیدواژه ها:

Clinical evaluation ، Experimental autoimmune encephalomyelitis ، GW-۴۰۵۸۳۳ ، Locomotor activity ، Multiple sclerosis ، Proinflammatory cytokines.