心肌炎
富马酸二甲酯
免疫学
医学
化学
计算生物学
内科学
生物
多发性硬化
作者
Marina Milenković,Nevena Arsenović-Ranin,Dragana Božić,Biljana Bufan,Ivan Jančić,Zorica Stojić-Vukanić
标识
DOI:10.1016/j.arcmed.2008.07.003
摘要
Fumaric acid esters (FAE) have been proven to be effective for the systemic treatment of psoriasis and multiple sclerosis, Th1 cell-mediated chronic inflammatory diseases, but their effect on autoimmune myocarditis has not yet been addressed. We investigated the effect of dimethyl fumarate (DMF) on myosin-induced experimental autoimmune myocarditis (EAM).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.Both early and late treatment with 15 mg/kg body weight (bw) DMF markedly 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 DMF-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.These results show for the first time that DMF ameliorates experimental autoimmune myocarditis and may be acted, at least in part, by interfering with the production of TNF-alpha.
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