Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration.
Fumaric acid esters (FAE) have proven their therapeutic efficacy in psoriasis, a Th1 mediated skin disease. More recently, preliminary data have suggested an activity in multiple sclerosis (MS) as well. To investigate further possible mechanisms of action of these compounds in inflammatory diseases, we studied the FAE methyl hydrogen fumarate (MHF) and dimethyl fumarate (DMF) in chronic experimental autoimmune encephalomyelitis (EAE) induced by immunization of C57BL/6 mice with MOG peptide aa 35-55. Preventive treatment with these FAE was delivered twice a day by oral gavage. Both esters had a significant therapeutic effect on the disease course and histology showed a strongly reduced macrophage inflammation in the spinal cord. Multiparameter cytokine analysis from blood detected an increase of IL-10 in the treated animals. We conclude that the underlying biological activity of FAE in EAE is complex and, to elucidate the molecular mechanisms, further investigation is needed.
Schilling
S
S
Institute for Multiple Sclerosis Research, University of Goettingen, Goettingen, Germany.
Goelz
S
S
Linker
R
R
Luehder
F
F
Gold
R
R
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D016207:Cytokines / Q000097:blood; D000069462:Dimethyl Fumarate; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation; D007378:Interleukins / Q000097:blood; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D015415:Biomarkers; D016207:Cytokines; D005650:Fumarates; D007166:Immunosuppressive Agents; D007378:Interleukins; C509058:monomethyl fumarate; D000069462:Dimethyl Fumarate