title: IFN-γ and TNF-α induce a different modulation of interleukin-6 in systemic sclerosis fibroblasts compared to healthy controls.
abstract: BACKGROUND
  To our knowledge, no previous study has evaluated the effect of interferon (IFN)-γ, tumour necrosis factor (TNF)-α, or their combination on the prototype proinflammatory cytokine interleukin (IL)-6 in primary cultured fibroblasts from patients with systemic sclerosis (SSc) at an early stage of the disease.
  
  
  METHODS
  Fibroblast cultures from five SSc patients (disease duration < 2 years) and five healthy controls were evaluated for the basal production of IL-6, and after stimulation with TNF-α or IFN-γ, alone or combined.
  
  
  RESULTS
  The fibroblasts from SSc patients produced higher levels of IL-6 in basal condition than controls [617 ± 173 vs. 213 ± 123 pg/mL; analysis of variance (ANOVA), p < 0.001]. TNF-α was able to dose-dependently induce IL-6 in SSc (609 ± 184, 723 ± 243, 1079 ± 297, 1436 ± 326 pg/mL, with TNF-α 0, 1, 5, 10 ng/mL, respectively) but not in control fibroblasts, whereas IFN-γ was unable to induce IL-6. Furthermore, the combination of IFN-γ and TNF-α induced a stronger secretion of IL-6 in SSc fibroblasts (ANOVA, p < 0.0001), without effect in controls.
  
  
  CONCLUSIONS
  SSc fibroblasts participate in the self-perpetuation of inflammation by releasing IL-6, under the influence of TNF-α and/or IFN-γ.
authors: Department of Internal Medicine, Metabolism Unit, University of Pisa School of Medicine, Pisa, Italy. a.antonelli@med.unipi.it
authors: A
authors: A
authors: Antonelli
authors: C
authors: C
authors: Ferri
authors: S M
authors: SM
authors: Ferrari
authors: C
authors: C
authors: Mancusi
authors: M
authors: M
authors: Colaci
authors: M
authors: M
authors: Sebastiani
authors: P
authors: P
authors: Fallahi
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma