Cytokine secretion pattern in treatment of lymphocytes of multiple sclerosis patients with fumaric acid esters

Immunol Invest. 2011;40(6):581-96. doi: 10.3109/08820139.2011.569626. Epub 2011 Apr 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Count
  • Cell Survival / drug effects
  • Cytokines / metabolism*
  • Dimethyl Fumarate
  • Female
  • Fumarates / pharmacology*
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Male
  • Maleates / pharmacology
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism*
  • Myelin Basic Protein / immunology
  • Myelin Basic Protein / pharmacology
  • Phytohemagglutinins / pharmacology
  • Th1 Cells / cytology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Young Adult

Substances

  • Cytokines
  • Fumarates
  • IL4 protein, human
  • MBP protein, human
  • Maleates
  • Myelin Basic Protein
  • Phytohemagglutinins
  • citraconic acid
  • Interleukin-4
  • Interferon-gamma
  • Dimethyl Fumarate