Dimethylfumarate for psoriasis: more than a dietary curiosity.
Fumaric acid esters (FAEs) have been used for the oral treatment of psoriasis since 1959 and have been registered for this indication in Germany since 1994. Dimethylfumarate (DMF) and its metabolite methylhydrogenfumarate (MHF) are the pharmacologically active compounds, with DMF being the main component of the marketed FAE-mixture. However, the mechanism of action of FAE is yet to be fully understood. It has been shown that DMF inhibits NFkappaB translocation, which leads to (i) the inhibition of pro-inflammatory cytokine production and adhesion molecule expression, (ii) the inhibition of dendritic cell differentiation and, at higher concentrations, (iii) the induction of apoptosis. Recent evidence also shows that these effects are mediated through the interference of the intracellular redox system by DMF. Here, the mode of action of FAE and its clinical use for psoriasis will be discussed.
Mrowietz
Ulrich
U
Department of Dermatology, University Clinic of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. umrowietz@dermatology.uni-kiel.de
Asadullah
Khusru
K
D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002454:Cell Differentiation; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology; D003879:Dermatologic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069462:Dimethyl Fumarate; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D021381:Protein Transport; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D003879:Dermatologic Agents; D005650:Fumarates; D016328:NF-kappa B; D000069462:Dimethyl Fumarate