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, 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).

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 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.

CONCLUSIONS:

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.

• Authors: Marina Milenković, Nevena Arsenović-Ranin, Dragana Vucićević, Biljana Bufan, Ivan Jancić, Zorica Stojić-Vukanić
• Journal: Archives of medical research (Arch Med Res) Vol. 39 Issue 7 Pg. 639-46 (Oct 2008) ISSN: 0188-4409 [Print] United States
• PMID: 18760191 (Publication Type: Journal Article)

Chemical References

• Fumarates
• Immunosuppressive Agents
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Myosins
• Dimethyl Fumarate

Topics

• Animals
• Autoimmune Diseases (drug therapy, immunology, pathology)
• Dimethyl Fumarate
• Disease Models, Animal
• Fumarates (administration & dosage, therapeutic use)
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Interleukin-10 (blood, metabolism)
• Lymphocytes (immunology, metabolism)
• Male
• Myocarditis (drug therapy, immunology, pathology)
• Myocardium (pathology)
• Myosins (immunology)
• Rats
• Tumor Necrosis Factor-alpha (blood, metabolism)