title: Sex differences in in vitro pro-inflammatory cytokine production from peripheral blood of multiple sclerosis patients.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York at Buffalo, 543 Cooke Hall, Buffalo, NY 14260-1200, USA.
authors.forename: Linh T
authors.initials: LT
authors.lastname: Nguyen
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Monika
authors.initials: M
authors.lastname: Baier
authors.forename: Carol
authors.initials: C
authors.lastname: Brownscheidle
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Jacobs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D017252:CD3 Complex / Q000096:biosynthesis; D018956:CD5 Antigens / Q000096:biosynthesis; D016207:Cytokines / Q000097:blood*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000276:immunology; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D017252:CD3 Complex; D018956:CD5 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma