Modulatory effect of celastrol on Th1/Th2 cytokines profile, TLR2 and CD3+T-lymphocyte expression in a relapsing-remitting model of multiple sclerosis in rats

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of brain and spinal cord that has an increasing incidence worldwide and classically presents in a relapsing-remitting form. This study was designed to induce a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE) to investigate the possible modulatory effect of celastrol On Th1 /Th2 cytokines profile, immunohistochemical expression of TLR2, and CD3+T-lymphocytic count. Eighteen female Sprague Dawley rats were divided into 3 groups; where group I served as normal control, group II as EAE +vehicle, and group III as EAE treated by celastrol (1 mg/kg/day, i.p.) started at 10th day till 42nd day post-immunization. The clinical score of rats in group II (EAE+vehicle) was relapsed after the re-challenge at the 35th clay post-immunization and exhibited significant positive association with serum NF-kappa B expression and nitrites levels in brain and spinal cord, and CD3+ T-lymphocylic count in brain tissues while serum IL-10 showed significant negative association. Treatment of EAE by celastrol caused amelioration of the clinical score and inhibited the relapse. It caused significant shift in cytokines profile from Th1 by decrease in INF-alpha towards Th2 pattern by increase in IL-10. Moreover, celastrol treatment resulted in significant reduction in NF-kappa B expression, nitrites levels, as well as immunohistochemical expression of TLR2 and CD3+ T-lymphocytic count. The beneficial effect of celastrol was further confirmed histopathologically by reduction in H&E score. Collectively, these results provide a promising pre-clinical evidence and conclusion about use of celastrol in treatment of multiple sclerosis that must be accessed in further clinical studies. (C) 2014 Elsevier B.V. All rights reserved,