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.
IFN-γ and TNF-α induce a different modulation of interleukin-6 in systemic sclerosis fibroblasts compared to healthy controls.
ANTONELLI, ALESSANDRO;Ferrari S;Fallahi P.
2011-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
