Edaravone inhibits collagen-induced arthritis possibly through suppression of nuclear factor-kappa B

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease which is induced by proinflammatory cytokines or oxidative stress. The activation of nuclear factor-kappa B (NF-kappa B) that contributed to imbalance between apoptosis and proliferation of rheumatoid synovial cells (SC). Edaravone, clinically available free radical scavenger in Japan, is confirmed to be beneficial in the acute stage of stroke. We aimed to investigate the suppressive effect of edaravone on collagen-induced arthritis (CIA) mice and on the activated molecules in SC stimulated by interleukin-1 beta (IL-1 beta). Methods: Edaravone was administrated intravenously at a dose of 3 mg/kg of body weight to CIA mice. The progression of CIA was evaluated by the macroscopic arthritis scoring system of paws. Interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3) concentrations in culture medium of human SC were measured by enzyme linked immunosorbent assays. Caspase-3/7 activity and nuclear factor-kappa B (NF-kappa B) protein level of cultured human SC were estimated by fluorometric assay and Western blot analysis, respectively. Results: Edaravone significantly decreased macroscopic arthritis score in CIA mice. Acceleration of IL-6 and MMP-3 productions and attenuation of caspase-3/7 activity in IL-1 beta-stimulated SC were abated by edaravone. Activated NF-kappa B in IL-1 beta-stimulated SC was suppressed by edaravone. Conclusion: Edaravone, antioxidants available for clinical use, appears to have therapeutic effect on RA. We suggest that the inhibitory effect of edaravone on RA might be exerted, at least in part, through suppression of activated NF-kappa B. Therefore, we expect therapeutical use of edaravone as an anti-rheumatic agent. (c) 2007 Elsevier Ltd. All rights reserved.