fumarates and monomethyl-fumarate

Tecfidera. The objective of this study was to determine whether two Bafiertam™ capsules each containing 95 mg of MMF is bioequivalent to one Tecfidera. This was a single-dose, open-label, randomized, two-way crossover study evaluating two treatments over two periods with a washout interval between treatments. Fifty healthy subjects were randomized to receive a single dose of the test drug MMF 190 mg as 2 × 95 mg delayed-release capsules or the reference drug DMF 240 mg as a 1 × 240-mg delayed-release capsule. Blood samples were obtained prior to dosing and at prespecified time points through 24 h post-dose to determine plasma concentrations of MMF. The pharmacokinetic parameters of MMF were calculated including maximum observed concentration, time to reach maximum observed concentration, apparent half-life of the drug in plasma, AUC. The geometric least-squares mean ratios (90% confidence interval) of the test drug MMF vs the reference drug DMF were 96.80% (92.18-101.64), 96.35% (91.81-101.12), and 104.84% (95.54-115.05) for AUC. Based on the statistical analysis results of the pharmacokinetic parameters of MMF, a single oral dose of two Bafiertam™ DR 95 mg capsules is bioequivalent to a single oral dose of one Tecfidera. This study was retrospectively registered with ClinicalTrials.gov (NCT04570670) on 30 September, 2020.

Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Capsules; Cross-Over Studies; Delayed-Action Preparations; Dimethyl Fumarate; Female; Fumarates; Half-Life; Humans; Immunosuppressive Agents; Male; Middle Aged; Therapeutic Equivalency

Monomethyl fumarate (MMF) is the pharmacologically active metabolite of dimethyl fumarate (DMF). MMF formulated as Bafiertam™ 190 mg and DMF formulated as Tecfidera 240 mg deliver bioequivalent exposure of MMF and therefore possess the same efficacy/safety profiles. DMF is a widely used oral treatment for relapsing-remitting forms of multiple sclerosis (RRMS) but is limited in some patients, primarily female, by issues with gastrointestinal (GI) tolerability.. This was a randomized, double-blind, head-to-head, 5-week study evaluating the GI tolerability of MMF 190 mg vs DMF 240 mg, administered twice daily in healthy subjects, using a derivative of the self-administered Modified Overall Gastrointestinal Symptom Scale (MOGISS). Subjects were stratified (3:1, female:male) and randomized (1:1) to the treatments. The primary endpoint was the Area Under the Curve (AUC) in each of the individual symptoms in the MOGISS over the 5-week treatment period. Other endpoints included the AUC over the 5-week treatment period in the MOGISS composite and total scores; duration and severity of GI events; Number and percentage of subjects reporting GI events during the overall treatment period, and assessment of safety/tolerability.. Inferential analysis of the hierarchical testing of overall treatment differences in each MOGISS symptom AUC occurred in a predefined sequence starting with Abdominal Pain. For each symptom, LSMean AUC values were lower for MMF than DMF, however, the first primary endpoint, Abdominal Pain, was not statistically different between treatments; thus, all subsequent statistical analyses were considered exploratory. The side effects and safety profiles observed were consistent with the known profiles of DMF, with no new or unique safety concerns noted.. Bafiertam showed an improved gastrointestinal tolerability profile compared with Tecfidera, with less severe GI events and fewer days of self-assessed GI symptoms, fewer GI adverse events, and lower discontinuation rates because of GI adverse events.

Topics: Dimethyl Fumarate; Female; Fumarates; Humans; Immunosuppressive Agents; Male; Multiple Sclerosis, Relapsing-Remitting

Dendritic cells (DCs) are important targets for eliciting allograft rejection after transplantation. Previous studies have demonstrated that metabolic reprogramming of DCs can transform their immune functions and induce their differentiation into tolerogenic DCs. In this study, we aim to investigate the protective effects and mechanisms of monomethyl fumarate (MMF), a bioactive metabolite of fumaric acid esters, in a mouse model of allogeneic heart transplantation. Bone marrow-derived DCs are harvested and treated with MMF to determine the impact of MMF on the phenotype and immunosuppressive function of DCs by flow cytometry and T-cell proliferation assays. RNA sequencing and Seahorse analyses are performed for mature DCs and MMF-treated DCs (MMF-DCs) to investigate the underlying mechanism. Our results show that MMF prolongs the survival time of heart grafts and inhibits the activation of DCs

Topics: Animals; Dendritic Cells; Fumarates; Graft Rejection; Heart Transplantation; Immune Tolerance; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory

Research has connected Parkinson's disease (PD) with impaired intestinal barrier. The activation of G-protein-coupled receptor 109A (GPR109A) protects the intestinal barrier by inhibiting the NF-κB signaling pathway. Sodium butyrate (NaB), which is a GPR109A ligand, may have anti-PD effects. The current study's objective is to demonstrate that NaB or monomethyl fumarate (MMF, an agonist of the GPR109A) can treat PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) via repairing the intestinal barrier. Male C57BL/6J mice were divided into four groups randomly: control, MPTP + vehicle, MPTP + NaB, and MPTP + MMF. Modeling mice received MPTP (20 mg/kg/day, i.p.) for a week, while control mice received sterile PBS. Then, four groups each received two weeks of sterile PBS (10 mL/kg/day, i.g.), sterile PBS (10 mL/kg/day, i.g.), NaB (600 mg/kg/day, i.g.), or MMF (100 mg/kg/day, i.g.). We assessed the expression of tight junction (TJ) proteins (occludin and claudin-1), GPR109A, and p65 in the colon, performed microscopic examination via HE staining, quantified markers of intestinal permeability and proinflammatory cytokines in serum, and evaluated motor symptoms and pathological changes in the substantia nigra (SN) or striatum. According to our results, MPTP-induced defected motor function, decreased dopamine and 5-hydroxytryptamine levels in the striatum, decreased tyrosine hydroxylase-positive neurons and increased activated microglia in the SN, and systemic inflammation were ameliorated by NaB or MMF treatment. Additionally, the ruined intestinal barrier was also rebuilt and NF-κB was suppressed after the treatment, with higher levels of TJ proteins, GPR109A, and decreased intestinal permeability. These results show that NaB or MMF can remedy motor symptoms and pathological alterations in PD mice by restoring the intestinal barrier with activated GPR109A. We demonstrate the potential for repairing the compromised intestinal barrier and activating GPR109A as promising treatments for PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Butyric Acid; Claudin-1; Cytokines; Disease Models, Animal; Dopamine; Fumarates; Ligands; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; NF-kappa B; Occludin; Parkinson Disease; Receptors, G-Protein-Coupled; Serotonin; Tyrosine 3-Monooxygenase

Topics: Apoptosis; Cells, Cultured; Dimethyl Fumarate; Fumarates; Humans; Leukocytes, Mononuclear; Neutrophils; Primary Cell Culture

Macrophage activation syndrome (MAS) is characterized by increased serum levels of ferritin and heme oxygenase 1 (HO-1), and yet no known function is ascribed to these molecules in MAS. Because HO-1 is antiinflammatory, we hypothesized that pharmacologic activation of HO-1 could ameliorate MAS disease activity. Dimethyl fumarate (DMF), a treatment approved by the US Food and Drug Administration for multiple sclerosis, activates HO-1. Monomethyl fumarate (MMF) is the active metabolite of DMF. We therefore evaluated whether MMF could elicit HO-1-dependent therapeutic improvements in a murine model of MAS.. We induced MAS by repeated activation of Toll-like receptor 9 (TLR-9) in wild-type and myeloid-specific HO-1-deficient mice. MMF was administered twice daily to test its efficacy. We assessed organ weights, serum cytokine levels, histologic features of the spleen and liver tissue, and complete blood cell counts to evaluate disease activity. Statistical testing was performed using Student's t-test or by 2-way analysis of variance as appropriate.. The presence of HO-1 was required for the majority of TLR-9-induced interleukin-10 (IL-10). IL-10 production in TLR-9-induced MAS was found to correlate with the myeloid-HO-1 gene dose in myeloid cells (P < 0.001). MMF treatment increased the levels of HO-1 in splenic macrophages by ~2-fold (P < 0.01), increased serum levels of IL-10 in an HO-1-dependent manner in mice with TLR-9-induced MAS (P < 0.005), and improved multiple disease parameters in both an HO-1-dependent and HO-1-independent manner.. TLR-9-induced production of IL-10 is regulated by HO-1 activity both in vitro and in vivo. Therapeutic enhancement of the HO-1/IL-10 axis in a murine model was able to significantly ameliorate MAS disease activity. These results suggest that HO-1 may be viable as a MAS therapeutic target, and treatment with DMF and MMF should be considered in future investigations of MAS therapy.

Topics: Animals; Cytokines; Disease Models, Animal; Fumarates; Heme Oxygenase-1; Interleukin-10; Liver; Macrophage Activation Syndrome; Macrophages; Membrane Proteins; Mice; Mice, Knockout; Oligodeoxyribonucleotides; Organ Size; Spleen; Toll-Like Receptor 9

Dimethyl fumarate (DMF) is a disease-modifying therapy for patients with relapsing-remitting multiple sclerosis (RRMS). T cells are major contributors to the pathogenesis of RRMS, where they regulate the pathogenic immune response and participate in CNS lesion development.. In this study we evaluate the therapeutic effects of DMF on T cell subpopulations, their CNS migration potential and effector functions.. Blood and CSF from untreated and DMF-treated patients with RRMS and healthy donors were analyzed by flow cytometry.. DMF reduced the prevalence of circulating proinflammatory CD4+ and CD8+ memory T cells, whereas regulatory T cells were unaffected. Furthermore, DMF reduced the frequency of CD4+ T cells expressing CNS-homing markers. In coherence, we found a reduced recruitment of CD4+ but not CD8+ T cells to CSF. We also found that monomethyl fumarate dampened T cell proliferation and reduced the frequency of TNF-α, IL-17 and IFN-γ producing T cells.. DMF influences the balance between proinflammatory and regulatory T cells, presumably favoring a less proinflammatory environment. DMF also reduces the CNS migratory potential of CD4+ T cells whereas CD8+ T cells are less affected. Altogether, our study suggests an anti-inflammatory effect of DMF mainly on the CD4+ T cell compartment.

Topics: Adult; Cell Proliferation; Cohort Studies; Cytokines; Dimethyl Fumarate; Female; Fumarates; Humans; Immunologic Factors; Inflammation; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; T-Lymphocytes; Young Adult

Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood.. To investigate the role of MMF on human mDCs maturation and function.. mDCs from healthy controls were isolated and cultured in vitro with MMF. The effect of MMF on mDC gene expression was determined by polymerase chain reaction (PCR) array after in vitro MMF treatment. The ability of mDCs to activate T cells was assessed by in vitro co-culture system. mDCs from DMF-treated multiple sclerosis (MS) patients were analyzed by flow cytometry and PCR.. MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB. mDCs from DMF-treated MS patients also showed the same immature phenotype. T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells.. We report that MMF can modulate immune response by affecting human mDC function.

Topics: Dendritic Cells; Dimethyl Fumarate; Fumarates; Humans; Immunologic Factors; Multiple Sclerosis, Relapsing-Remitting; Myeloid Cells; T-Lymphocytes

Dimethyl fumarate (DMF) is a disease-modifying therapy used for patients with relapsing-remitting multiple sclerosis (RRMS). B cells are important contributors to the pathogenesis of RRMS, where they regulate the inflammatory immune responses and participate in development of lesions in the central nervous system (CNS). The impact of DMF on B cell subpopulations remains incompletely understood.. In this study, we evaluated the effects of DMF on B cell subpopulations and their effector functions.. Blood from 21 DMF-treated and 18 untreated patients with RRMS was analyzed by flow cytometry.. We found that DMF reduces the frequency of circulating antigen-experienced B cells, a reduction likely related to a reduced frequency of follicular helper T (T. In summary, these data suggest an anti-inflammatory role of DMF and its metabolite MMF on the B cell compartment.

Topics: Adult; B-Lymphocytes; Cytokines; Dimethyl Fumarate; Female; Fumarates; Humans; Immunologic Factors; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; T-Lymphocytes, Helper-Inducer; Treatment Outcome; Young Adult

Monomethyl fumarate (MF) exerts anti-inflammatory and antioxidant capacities. Whether microRNA-139 and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) are involved in the pharmacological activity of MF remain unclear. We aim to elucidate the potential function of MF in intracerebral hemorrhage (ICH), and its possible mechanism.. Twenty-four Sprague Dawley (SD) rats were randomly assigned into sham group, ICH group and MF group, with 8 rats in each group. Rats in ICH and MF group were subjected to ICH procedures. Rat brain tissues were harvested at 48 h after ICH procedures. Evans blue extravasation was performed to evaluate ICH-induced rat brain damage. Content of cerebral edema and neurological deficit were examined to reflect the neuronal pathological lesions. Reactive oxygen species (ROS) content in rat brain was examined by immunofluorescence. Activities of oxidative stress indexes in rat brain homogenate were detected using relative commercial kits. MicroRNA-139 expression in rat brain was quantified by quantitative Real-time polymerase chain reaction (qRT-PCR). Finally, protein levels of Nrf2, HO-1, NQO1 and nuclear factor-kappa B (NF-κB) in rat brain tissues were examined by Western blot.. Compared with rats in sham group, neurological deficit scores of rats in ICH group were lower. Disruption of blood-brain barrier and brain tissue edema of rats were pronounced in ICH group. However, MF pretreatment markedly alleviated the above mentioned cerebral lesions. In addition, MF pretreatment increased activities of SOD, GSH and CAT, but decreased MDA and ROS contents in rat brain homogenate relative to those in ICH group (p<0.05). Western blot analysis found that expression levels of Nrf2, HO-1 and NQO-1 were markedly upregulated after MF pretreatment, while the expression level of NF-κB was downregulated. At the cellular level, we altered microRNA-139 expression in SH-SY5Y cells by transfection of microRNA-139 mimics or inhibitor. Overexpression of microRNA-139 remarkably increased Nrf2 expression and decreased NF-κB expression. Treatment of high-dose MF upregulated Nrf2, downregulated NF-κB and decreased ROS content in SH-SY5Y cells.. MF protects ICH in rats by inhibiting oxidative stress and inflammatory response through activating microRNA-139/Nrf2 axis.

Topics: Animals; Anti-Inflammatory Agents; Brain; Cell Line, Tumor; Cerebral Hemorrhage; Disease Models, Animal; Fumarates; Humans; MicroRNAs; Neurons; NF-E2-Related Factor 2; Oxidative Stress; Rats; Signal Transduction

Neutrophil (polymorphonuclear) granulocytes (PMN) have been shown to contribute to the pathogenesis of psoriasis by releasing interleukin-17 and LL37-DNA complexes via neutrophil extracellular traps (NETs), webs of chromatin strands decorated with antimicrobial peptides, in psoriatic skin. Fumaderm. To elucidate the effect of FAE treatment on human psoriasis and healthy donor NET formation.. Among the compounds present in the FAE formulation, dimethyl fumarate (DMF) pretreatment of human psoriasis and healthy donor PMN resulted in a consistent inhibitory effect on NET formation in response to phorbol 12-myristate 13-acetate but not to platelet activating factor and ionomycin. This effect was l-glutathione (GSH) dependent and involved a decrease in reactive oxygen species (ROS) production, a key event in NET formation. In contrast, G-protein-coupled signalling and protein synthesis were not involved. Monomethyl fumarate (MMF) was found to slightly reduce ROS production without affecting NET formation.. We report DMF as a potent, stimulus-specific, GSH- and ROS-dependent modulator of NET formation. Our results support the notion that modulation of NET formation contributes to the beneficial effects of FAEs in a variety of inflammatory conditions.

Topics: Analysis of Variance; Antioxidants; Caspases; Cells, Cultured; Dermatologic Agents; Dimethyl Fumarate; Dose-Response Relationship, Drug; Extracellular Traps; Fumarates; Glutathione; GTP-Binding Proteins; Humans; Ionomycin; Platelet Activating Factor; Psoriasis; Reactive Oxygen Species; Superoxides; Tetradecanoylphorbol Acetate

Dimethyl fumarate (DMF) is used successfully to treat psoriasis. In spite of its proven clinical efficacy, the mode of metabolism and the pharmacodynamics of DMF are still not completely understood. Some previous studies have indicated that orally applied DMF for a considerable part is quickly hydrolysed to methylhydrogen fumarate (MHF) at basic pH conditions as present in the upper intestine, especially in the presence of biological fluids containing esterases. On the other hand it was shown that DMF due to its high lipophilicity rapidly penetrates into cells and may thus at least in part be absorbed after po application without being hydrolysed. On the other hand, no detectable amounts of DMF were hitherto found in plasma samples after po administration. In order to shed light on possible further routes of presystemic metabolism of DMF, studies on the reactivity towards glutathione (GSH) were carried out. GSH is present in millimolar concentrations in almost all cells. DMF due to its nature as an alpha,beta-unsaturated carboxylic acid ester can react spontaneously with thiols via a Michael-type addition. It could be shown that DMF reacts at high rates under near-physiological conditions. Studies on the reaction kinetics at pH 7.4 show that GSH addition proceeds rapidly to yield a 1:1 mixture of both diastereomeric 2-(S-glutathionyl)-succinic acid dimethyl esters. MHF under identical conditions was shown to react with GSH as well leading to a mixture of four products (2 diastereomeric pairs). However, MHF reacted at a much lower rate. The structures of all thiol conjugates were confirmed unambiguously by extensive NMR measurements. GSH conjugates and the corresponding mercapturic acids on grounds of the high spontaneous reactivity observed may be expected to be major metabolites of unhydrolysed DMF which makes its way into enterocytes. On the other hand, MHF, due to its slow reaction with GSH, may have higher chances than DMF to react with more essential thiol groups in macromolecules.

Topics: Acetylcysteine; Dimethyl Fumarate; Esters; Fumarates; Glutathione; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Molecular Structure; Sensitivity and Specificity; Succinates; Time Factors

Psoriasis is a chronic inflammatory skin disorder in which T-cell-mediated immune responses are thought to play a prominent role. Fumaric acid esters (FAEs) have proved to be an effective systemic treatment for psoriasis. The FAE dimethylfumarate (DMF) strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells. Additionally, it has been demonstrated that the nuclear translocation of the activated transcription factor nuclear factor kappaB (NF-kappaB) is inhibited in human endothelial cells and fibroblasts activated with tumour necrosis factor-alpha. The NF-kappaB pathway plays a major role in regulating inflammatory cytokine production as well as in cell differentiation and apoptosis. T-cell survival is also dependent on the activation of NF-kappaB and it has been demonstrated in vitro that DMF is an inducer of apoptosis in human T cells. The influence of FAEs on the expression of nuclear transcription factors in T cells has not yet been investigated.. The effects of DMF and its main metabolite, methylhydrogenfumarate (MHF), were assessed on the nuclear binding of NF-kappaB, nuclear factor of activated T cells (NF-AT) and CCAAT/enhancer binding protein beta (C/EBPbeta) in purified human T cells.. To examine the effect of DMF and MHF on the nuclear binding of NF-kappaB, NF-AT and C/EBPbeta in human T cells and fibroblasts, an enzyme-linked immunosorbent assay (ELISA) was used. The binding activity of these transcription factors was measured by its absorbance in an ELISA plate reader at 450 nm. Conspicuous results were confirmed by performing electrophoretic mobility shift assays.. DMF inhibited nuclear binding of NF-kappaB1, but not of NF-AT or C/EBPbeta, in purified human T cells. No effect of MHF on any of these transcription factors could be seen. To verify our results, we used the same assay to show the inhibitory effect on the nuclear binding of NF-kappaB1 in human fibroblasts (as previously published).. The results of this study provide evidence for a specific effect of DMF on NF-kappaB. The data support previous results where NF-kappaB-dependent mediators and surface molecules were suppressed by DMF, but not those activated by other nuclear transcription factors.

Topics: CCAAT-Enhancer-Binding Protein-beta; Dimethyl Fumarate; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Fumarates; Humans; Immunosuppressive Agents; NF-kappa B; NFATC Transcription Factors; T-Lymphocytes

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.

Topics: Candida albicans; Cells, Cultured; Cytochrome c Group; Dermatologic Agents; Dimethyl Fumarate; Escherichia coli; Fumarates; Humans; Phagocytes; Staphylococcus aureus; Superoxides; Zymosan

Fumaric acid esters (FAE) have proven their therapeutic efficacy in psoriasis, a Th1 mediated skin disease. More recently, preliminary data have suggested an activity in multiple sclerosis (MS) as well. To investigate further possible mechanisms of action of these compounds in inflammatory diseases, we studied the FAE methyl hydrogen fumarate (MHF) and dimethyl fumarate (DMF) in chronic experimental autoimmune encephalomyelitis (EAE) induced by immunization of C57BL/6 mice with MOG peptide aa 35-55. Preventive treatment with these FAE was delivered twice a day by oral gavage. Both esters had a significant therapeutic effect on the disease course and histology showed a strongly reduced macrophage inflammation in the spinal cord. Multiparameter cytokine analysis from blood detected an increase of IL-10 in the treated animals. We conclude that the underlying biological activity of FAE in EAE is complex and, to elucidate the molecular mechanisms, further investigation is needed.

Topics: Animals; Biomarkers; Cell Count; Cytokines; Dimethyl Fumarate; Encephalomyelitis, Autoimmune, Experimental; Female; Fumarates; Immunosuppressive Agents; Inflammation; Interleukins; Macrophages; Mice; Mice, Inbred C57BL; Spinal Cord; T-Lymphocytes

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.

Topics: Candida albicans; Cell Survival; Dexamethasone; Dimethyl Fumarate; Escherichia coli; Fumarates; Humans; Lectins, C-Type; Mannose Receptor; Mannose-Binding Lectins; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Opsonin Proteins; Phagocytosis; Receptors, Cell Surface; Staphylococcus aureus; Superoxides; Up-Regulation; Zymosan