Cytokine Secretion Pattern in Treatment of Lymphocytes of Multiple Sclerosis Patients with Fumaric Acid Esters

Abstract

The present study was performed to investigate the effects of dimethylfumarate (DMF) and methylhydrogen fumarate (MHF) on the cytokine pattern of peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients. The PBMCs from patients and healthy controls were stimulated with myelin basic protein (MBP) or phytohemagglutinin (PHA) and cultured in the presence of DMF and MHF. The percentage of CD4+IL-4+ and CD4+IFN-γ+ cells was determined by means of intracellular cytokine staining. CD4+IL-4+ cells were significantly increased in the presence of DMF and MHF when PBMCs were stimulated by MBP (P < 0.003). The same significant result was obtained by PHA stimulation (P < 0.049). In terms of CD4+IFN-γ+ cells, the percentage of cells did not significantly differ between the cultures stimulated with MBP or PHA in the presence and absence of the drugs. Results of MBP stimulation in control group also showed a significant increase in CD4+IL-4+ cells in the presence of DMF and MHF. In comparison between patient and control groups, no statistically significant changes were observed. In conclusion, both DMF and MHF effectively increased IL-4 production, whereas they did not significantly change IFN-γ level, indicating the role of these drugs in increasing the production of beneficial cytokines such as IL-4.

Immunopathology of multiple sclerosis

“…T H 1 cells and T H 17 cells are the main CD4 + T cell subsets implicated in disease, and thus skewing of T cell differentiation away from these subsets and towards a T H 2 cell phenotype has been a prominent therapeutic concept and is considered to be a mechanism of action of the first-line, disease-modifying therapies IFNβ 56 , glatiramer acetate (Copaxone; Teva and Sanofi-Aventis) 57 and dimethyl fumarate (Tecfidera; Biogen) 58 .…”

Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE Mouse Model of Multiple Sclerosis

“…To date several candidate therapeutic agents have been tested for their beneficial effect in EAE model that allows investigation of demyelination processes dependent of T-cell-mediated inflammation (Abtahi Froushani et al, 2014;Bai et al, 2011;Moon et al, 2011;Shin & Matsumoto, 2001;Shin et al, 2000, Zoghi et al, 2011Wang et al, 2009). Even though considerable efforts were undertaken in the MS research field during the past decades, the exact cause of multiple sclerosis is still unknown and the therapeutic treatments are limited.…”

Dimethyl Fumarate Modulation of Immune and Antioxidant Responses: Application to HIV Therapy

“…Both DMF and MMF increased the production of multiple Th2 cytokines (IL-4, IL-10) 47–49 in T-lymphocytes. Furthermore, DMF, but not MMF, suppressed Th1 cytokine (IFN-γ) release and chemokine receptor (CXCR3) expression, as well as the skin-homing chemokine receptor CCR10.…”