Tropisetron diminishes demyelination and disease severity in an animal model of multiple sclerosis.

Abstract Tropisetron, a selective 5-HT3 receptor (5-HT3R) antagonist, has been widely used to counteract chemotherapy-induced emesis. New investigations described the immunomodulatory properties of tropisetron which may not be 5HT3R mediated. In the present study, we assessed the potential effects of tropisetron on an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). EAE was induced in C57BL/6 mice by myelin oligodendrocyte glycoprotein peptide (MOG 35-55 ) immunization. Animals were treated with tropisetron (5 mg/kg/day); m-chlorophenylbiguanide (mCPBG), a selective 5-HT3R agonist (10 mg/kg/day); tropisetron (5 mg/kg/day) plus mCPBG (10 mg/kg/day), and granisetron (5 mg/kg/day) intraperitoneally on days 3–35 post-immunization. Treatment with tropisetron and granisetron markedly suppressed the clinical symptoms of EAE ( p p in vivo tropisetron, granisetron or tropisetron plus mCPBG therapy greatly reduced in vitro MOG 35-55 -stimulated proliferation of mononuclear cells from spleens, and MOG 35-55 -induced IL-2, IL-6 and IL-17 production by splenocytes isolated from EAE-induced mice ( p