Dimethyl fumarate (DMF) is a treatment for moderate-to-severe psoriasis and multiple sclerosis. DMF therapy typically improves skin inflammation within the first 3 months of treatment. DMF is a prodrug that generates the hydroxycarboxylic acid receptor 2 (HCA2) agonist, monomethyl fumarate (MMF). Despite widespread clinical use, DMF's mechanism of action is not fully understood.We wished to characterize the changes induced by DMF in peripheral neutrophils within the 3 months of treatment to better understand its early anti-psoriatic effects.Flow cytometry was used to assess T cell and neutrophil frequencies, apoptosis and activation phenotype. In vitro culture of neutrophils with DMF and MMF was used to evaluate apoptosis and HCA2 internalisation. Serum levels of neutrophil degranulation products were measured by ELISA.Baseline psoriasis patients had significantly higher leukocyte counts compared to controls, with a large population of pro-inflammatory CD62Llo CD11bbright neutrophils. Analysis revealed that DMF treatment reduced the frequency of CD62Llo CD11bbright neutrophils and serum levels of neutrophil activation markers. This reduction was not linked to increased apoptosis.Our results reveal a novel in vivo effect of DMF therapy on pro-inflammatory neutrophils that likely contributes to this treatment's anti-psoriatic efficacy.
P J Morrison, I Suhrkamp, S Gerdes, U Mrowietz