Mycophenolate mofetil improves neurological function and alters blood T-lymphocyte subsets in rats with experimental autoimmune encephalomyelitis

Abstract

Objective This study evaluated the clinical and pathological effects of the immunosuppressive agent mycophenolate mofetil (MMF) in rats with experimental autoimmune encephalomyelitis (EAE; a model of multiple sclerosis [MS]). Methods EAE rats were randomly divided into 4 groups: model alone ( n = 7); low- or high-dose MMF (20 and 30 mg/kg per day, respectively, n = 6 each) orally for 14 days; methylprednisolone (20 mg/kg per day, n = 6) injected once daily for 3 days. Six normal Wistar rats served as controls. Clinical signs and histopathological findings were evaluated 14 days after treatment started. Results Oral administration of high-dose MMF significantly ameliorated the course of EAE in rats: cumulative clinical scores were lower and weight loss was less than in rats receiving methylprednisolone. The ameliorated disease course was associated with alleviation of histopathological signs of EAE. Treatment increased the blood proportion of CD8+, CD4+CD25+ and CD4+CD45RA+ T cells, with a concomitant reduced proportion of CD4+ T cells and ratio of CD4+ to CD8+ T cells, compared with EAE model alone rats. Conclusions MMF may have pharmacological potential in MS treatment and these findings may help in understanding the pathophysiological mechanism of MS.