[Modulatory effect of fumaric acid esters on superoxide-anion generation in human phagocytes].
Fumaric acid esters (FAE), mainly dimethylfumarate (DMF), have been shown to be highly efficacious in the treatment of psoriasis. Among the potential side effects of FAE therapy, lymphocytopenia is sometimes observed. In order to address the question whether FAE may interfere with systems of the innate defense, the modulatory role of FAE on the generation of superoxide-anion by human monocytes and neutrophils was studied by measuring the reduction of cytochrome c. Various concentrations of DMF and its metabolite methylhydrogenfumarate (MHF) were used to observe their modulatory effect on superoxide-anion generation by monocytes and neutrophils in response to bacteria (S. aureus and E. coli) and candida (C. albicans). Dexamethasone (DXM, 1 x 10(-7) mol x L(-1)) was also studied at the same time. We found that DXM significantly inhibited superoxide-anion generation from monocytes in response to bacteria and C. albicans, whereas DMF and MHF (10-20 microg x mL(-1)) significantly increased the production of superoxide-anion in monocytes in response to the above mentioned bacteria. DXM, DMF and MHF did not affect superoxide-anion generation of neutrophils. Our data indicate that DMF and MHF enhance superoxide-anion generation in human monocytes as one of the important mechanisms of innate defense against microorganisms.
Zhu
Ke-jian
KJ
Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China.
Cen
Jian-ping
JP
Lin
Ai-hua
AH
Jin
Na
N
Cheng
Hao
H
D002176:Candida albicans / Q000276:immunology; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D003879:Dermatologic Agents / Q000494:pharmacology; D000069462:Dimethyl Fumarate; D004926:Escherichia coli / Q000276:immunology; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D010586:Phagocytes / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*; D015054:Zymosan / Q000276:immunology
D003574:Cytochrome c Group; D003879:Dermatologic Agents; D005650:Fumarates; D013481:Superoxides; C076615:cytochrome c''; C509058:monomethyl fumarate; D015054:Zymosan; D000069462:Dimethyl Fumarate