Sex differences in in vitro pro-inflammatory cytokine production from peripheral blood of multiple sclerosis patients

J Neurol Sci. 2003 May 15;209(1-2):93-9. doi: 10.1016/s0022-510x(03)00004-2.


We compared the patterns of the pro-inflammatory cytokines, interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokines, interleukin-10 (IL-10) and tumor growth factor-beta (TGF-beta) from peripheral blood of male and female patients with relapsing-remitting (RR) and secondary progressive (SP) forms of multiple sclerosis (MS). The relationships between pro-inflammatory cytokines and disability (expanded disability status scale, EDSS) were also examined. Peripheral blood anti-coagulated with heparin was obtained from 47 MS patients (30 women and 17 men) and activated with phorbol-12-myristate 13 acetate (PMA) and ionomycin in the presence of brefeldin A and stained for flow cytometry with fluorescently labeled antibodies against intracellular IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-10. The T cells were delineated with peridinin chlorophyll protein (Per-CP) labeled anti-CD3 antibody. The stained samples were analyzed on a flow cytometer to assess the intracellular pro-inflammatory cytokine patterns. The levels of interleukin-10 (IL-10) and tumor growth factor-beta (TGF-beta) were measured in plasma using enzyme-linked immunoassay. The percentage of TNF-alpha-producing CD3 positive cells was significantly higher (P=0.045) in men (mean+/-S.D., 39+/-13%) than in women (mean+/-S.D., 29+/-13%) RR-MS patients. The percentage of CD3 positive cells producing IFN-gamma was significantly correlated with EDSS in females but not in males (Spearman rank correlation r(S)=0.49, P=0.018). The secretion of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha, is influenced by gender in MS patients and may contribute to the sexual dimorphism of MS.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • CD3 Complex / biosynthesis
  • CD5 Antigens / biosynthesis
  • Cytokines / blood*
  • Disability Evaluation
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Interleukin-4 / blood
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / blood*
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Sex Factors
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transforming Growth Factor beta / blood
  • Tumor Necrosis Factor-alpha / analysis


  • CD3 Complex
  • CD5 Antigens
  • Cytokines
  • Inflammation Mediators
  • Interleukin-2
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma