Beneficial effects of dimethyl fumarate on experimental autoimmune myocarditis

Abstract

Background. Fumaric acid esters (FAE) have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis, Thl cell-mediated chronic inflammatory diseases, but their effect on autoimmune rnyocarditis has not yet been addressed. We investigated the effect of dimethyl fumarate (DMF) on myosin-induced experimental autoimmune myocarditis (EAM). Methods. Dark Agouti (DA) rats immunized with porcine cardiac myosin were orally treated with 5 and 15 mg/kg body weight (bw) DMF either from days 0-10 (early treatment groups) or from days 10-21 (late treatment groups) after induction of EAM. All rats were sacrificed on day 21 after immunization and hearts were evaluated macroscopically and microscopically. Levels of TNF-alpha and IL-10 in serum and lymph node cells culture supernatants were detected by ELISA. Results. Both early and late treatment with 15 mg/kg body weight (bw) DMF markedly C, reduced the severity of myocarditis by comparing the incidence, heart weight bw ratio, macroscopic and microscopic scores, and number of OX-6+ cells in the myocardium. Further, levels of tumor necrosis factor-alpha (TNF-alpha) in serum and culture supernatants of lymph node cells stimulated with ConA or myosin were significantly lower in DNIF-treated EAM animals compared with vehicle-treated EAM rats. There was no significant difference in serum levels of interleukin-10 between DMF- and vehicle-treated EAM rats. Conclusions. These results show for the first time that DMF ameliorates experimental autoimmune rnyocarditis and may be acted, at least in part, by interfering with the production of TNF-alpha.