Department of Internal Medicine, Metabolism Unit, University of Pisa School of Medicine, Pisa, Italy.
Scand J Rheumatol. 2011 Nov;40(6):453-6. doi: 10.3109/03009742.2011.585349. Epub 2011 Jul 4.
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.
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.
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.
SSc fibroblasts participate in the self-perpetuation of inflammation by releasing IL-6, under the influence of TNF-α and/or IFN-γ.
据我们所知，以前的研究尚未评估在疾病早期的系统性硬化症（SSc）患者的原代成纤维细胞中，干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α 或它们的组合对原型促炎细胞因子白细胞介素（IL）-6 的影响。
评估了来自五名 SSc 患者（疾病持续时间<2 年）和五名健康对照者的成纤维细胞的 IL-6 的基础产生，并在单独或联合使用 TNF-α 或 IFN-γ 刺激后进行评估。
SSc 患者的成纤维细胞在基础条件下产生的 IL-6 水平高于对照组[617±173 与 213±123 pg/mL；方差分析（ANOVA），p<0.001]。TNF-α能够以剂量依赖性方式诱导 SSc 中的 IL-6（609±184、723±243、1079±297、1436±326 pg/mL，分别用 TNF-α 0、1、5、10 ng/mL），但不能诱导对照组的成纤维细胞中产生 IL-6，而 IFN-γ不能诱导 IL-6 的产生。此外，IFN-γ 和 TNF-α 的组合在 SSc 成纤维细胞中诱导更强的 IL-6 分泌（ANOVA，p<0.0001），而在对照组中没有影响。
SSc 成纤维细胞在 TNF-α 和/或 IFN-γ 的影响下通过释放 IL-6 参与炎症的自我延续。
