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Enhancement of antibacterial superoxide-anion generation in human monocytes by fumaric acid esters
1Department of Dermatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qing Chun Road, Hangzhou 310009, People's Republic of China. zhukejian@mail.hz.zj.cn
Abstract:
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.
Insights
Dimethylfumarate (DMF) and methylhydrogenfumarate (MHF) may increase superoxide anion production in monocytes, a key part of innate immunity. However, these fumaric acid esters (FAE) do not impair the innate defense against microbial infections.
Area of Science:
- Immunology
- Pharmacology
Background:
- Fumaric acid esters (FAE) are effective systemic treatments for psoriasis.
- Lymphocytopenia is a potential side effect of FAE therapy.
- Understanding FAE effects on immune cells is crucial for patient safety.
Purpose of the Study:
- To investigate the impact of dimethylfumarate (DMF) and methylhydrogenfumarate (MHF) on human monocyte and neutrophil function.
- To assess the effects of DMF and MHF on superoxide anion generation and mannose receptor expression.
- To compare the effects of DMF and MHF with dexamethasone.
Main Methods:
- Human monocytes and neutrophils were stimulated with bacteria (Staphylococcus aureus, Escherichia coli), Candida albicans, zymosan, and fMLP.
- Superoxide anion generation was measured using luminol-dependent chemiluminescence.
- Mannose receptor expression was analyzed by flow cytometry.
Main Results:
- Dexamethasone inhibited monocyte superoxide anion generation in response to bacteria and C. albicans.
- DMF and MHF dose-dependently increased monocyte superoxide anion production stimulated by zymosan, fMLP, and bacteria.
- Neither DMF, MHF, nor dexamethasone affected neutrophil superoxide anion generation or monocyte mannose receptor expression.
Conclusions:
- DMF and MHF do not compromise the innate immune defense mechanism of superoxide anion production against microorganisms.
- The observed increase in monocyte superoxide anion generation by DMF and MHF warrants further investigation in the context of psoriasis treatment.
- These findings contribute to a better understanding of the immunological effects of fumaric acid esters in psoriasis therapy.
