Synergistic effects of atorvastatin and all-trans retinoic acid in ameliorating animal model of multiple sclerosis

Abstract

One suitable approach to enhancing multiple sclerosis (MS) treatment is combination of available medications to provide more desirable outcomes. Immunomodulatory effects of atorvastatin and/or all-trans retinoic acid (ATRA) were determined in previous studies. The present study was set out to investigate the synergistic effects of combination therapy by suboptimal doses of atorvastatin and ATRA in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. EAE was induced by MOG35–55 in female C57BL/6 mice. Therapies were initiated at day 12 post immunization when the mice developed a disability score and continued throughout the study until the day 33 when animals were sacrificed. Therapeutic treatment with half doses of atorvastatin and ATRA in combination has synergistic benefits causing the regression of clinical and neuropathological features of EAE more favorable than treatment with full doses of either drug alone. Without any advantage in anti-proliferative effect, combination treatment significantly reduced the secretion of pro-inflammatory cytokine interleukin-17 and conversely, increased the production of anti-inflammatory cytokine interleukin-10 more prominent than either drug alone. Furthermore, FoxP3+Treg cells were significantly increased only in combination treatment. In conclusion, combined atorvastatin and ATRA have immunomodulatory synergistic benefits and this pharmacological approach may be as a useful strategy to control MS.