In Vitro Effects of Sodium Benzoate on Th1/Th2 Deviation in Patients with Multiple Sclerosis

Immunol Invest. 2016 Oct;45(7):679-91. doi: 10.1080/08820139.2016.1208216. Epub 2016 Sep 9.


Interleukin 4 (IL-4) can improve the clinical manifestations in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). Sodium benzoate (NaB) deviates the cytokine profile to Th2 (or IL-4 producing) cells in EAE and thus might be effective in the treatment of MS. Therefore, in this study the effect of different concentrations of NaB on the percentage and mRNA levels of IL-4 and interferon gamma (IFN-γ)-producing peripheral blood mononuclear cells (PBMCs) of 20 Relapsing-remitting multiple sclerosis (RR-MS) patients and eight healthy controls was evaluated in the presence of mitogen (phytohemagglutinin, PHA) or specific antigen (myelin basic protein, MBP). Our results showed that in the patient's group the percentage of CD4(+)IL-4(+) cells was significantly increased in the presence of all concentrations of NaB when PBMCs were stimulated by MBP (p = 0.001) or PHA (p < 0.03). The same results were obtained for normal donors in the highest concentration of NaB, 1000 µg/ml (p = 0.02). Moreover, in the patient's group the percentage of CD4(+)IFN-γ(+) cells was decreased significantly when the PBMCs were stimulated by PHA and NaB (p < 0.004) or by MBP and 1000 µg/ml of NaB (p < 0.03). The effect of NaB on IL-4 and IFN-γ production was also documented at the mRNA levels. In conclusion, our data suggest that NaB is able to induce IL-4 production by human PBMCs and therefore might be a useful candidate for conjunctive therapy in RR-MS.

Keywords: IFN-γ; IL-4; Th1; Th2; multiple sclerosis; sodium benzoate.

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Myelin Basic Protein / immunology
  • Sodium Benzoate / pharmacology*
  • Sodium Benzoate / therapeutic use
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1-Th2 Balance* / drug effects
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Young Adult


  • Immunologic Factors
  • Myelin Basic Protein
  • Interleukin-4
  • Interferon-gamma
  • Sodium Benzoate