Enhancement of antibacterial superoxide-anion generation in human monocytes by fumaric acid esters

Fumaric acid esters (FAE) are used for the systemic therapy of psoriasis with high clinical efficacy. Among the potential side effects of FAE therapy, lymphocytopenia is sometimes observed. We have investigated the effect of dimethylfumarate (DMF) and its main metabolite methylhydrogenfumarate (MHF) as well as dexamethasone on superoxide anion generation by human monocytes and neutrophils after stimulation with bacteria (Staphylococcus aureus and Escherichia coli) and the yeast Candida albicans in addition with zymosan particles and with the tripeptide fMLP. Expression of mannose receptors on monocytes and neutrophils was also analyzed. The results showed that dexamethasone significantly inhibited superoxide anion generation from monocytes in response to bacteria and C. albicans, whereas DMF as well as MHF dose dependently increased the production of superoxide anion in monocytes in response to zymosan, fMLP and bacteria. Dexamethasone, DMF or MHF did not modulate superoxide anion generation of neutrophils. Expression of mannose receptors on monocytes was not regulated by DMF or MHF. Our data provide evidence that DMF and MHF do not alter the production of superoxide anions as an important mechanism of innate defense against microorganisms.