Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Rheumatology (Oxford). 2011 Feb;50(2):293-8. doi: 10.1093/rheumatology/keq330. Epub 2010 Nov 8.
IFN-α has been used to treat patients with Behçet's disease (BD). Recent studies have implicated the IL-23/Th-17 pathway in the pathogenesis of BD. In this study, we investigated whether IFN-α could affect this pathway.
Peripheral blood mononuclear cells (PBMCs) obtained from patients with active BD and controls were cultured alone or with IFN-α and the levels of IL-17 and IL-10 in the supernatants were measured by ELISA. Similar experiments were performed with isolated CD4(+) T cells from controls. The levels of phosphorylated STAT1 (p-STAT1), p-STAT2, p-STAT3 and p-STAT5 in CD4(+) T cells from controls cultured with or without IFN-α were also evaluated by ELISA. Furthermore, an experiment using anti-IL-10 was performed to examine underlying mechanisms of action of IFN-α.
Significantly higher levels of IL-17 and IL-10 were observed in the supernatants of PBMCs from BD patients as compared with controls. IFN-α significantly decreased IL-17 production by PBMCs from both patients and controls. On the other hand, IFN-α increased IL-10 production by PBMCs from patients and controls. Similar findings were obtained when using CD4(+) T cells from controls, IFN-α significantly increased p-STAT2 expression in control CD4(+) T cells. Anti-IL-10 antibody was able to neutralize the inhibitory effect of IFN-α on IL-17 by 35% as compared with controls.
In vitro experiments showed that IFN-α could inhibit IL-17 expression and increased IL-10 production by PBMCs and CD4(+) T cells. The inhibitory role of IFN-α on IL-17 was partly mediated by IL-10. IFN-α activity was mediated via STAT2 phosphorylation.
IFN-α 已被用于治疗贝切特病（BD）患者。最近的研究表明，IL-23/Th-17 通路在 BD 的发病机制中起作用。在这项研究中，我们研究了 IFN-α 是否会影响这条通路。
从活动期 BD 患者和对照者中分离外周血单个核细胞（PBMCs），单独或与 IFN-α 一起培养，通过 ELISA 测量上清液中 IL-17 和 IL-10 的水平。在对照者中也进行了用分离的 CD4(+) T 细胞进行的类似实验。通过 ELISA 还评估了对照者中用或不用 IFN-α 培养的 CD4(+) T 细胞中磷酸化 STAT1（p-STAT1）、p-STAT2、p-STAT3 和 p-STAT5 的水平。此外，进行了一项使用抗 IL-10 的实验，以研究 IFN-α 的作用机制。
与对照者相比，BD 患者 PBMCs 的上清液中观察到更高水平的 IL-17 和 IL-10。IFN-α 显著降低了来自患者和对照者的 PBMCs 中 IL-17 的产生。另一方面，IFN-α 增加了来自患者和对照者的 PBMCs 中 IL-10 的产生。在使用对照者的 CD4(+) T 细胞时也得到了相似的发现，IFN-α 显著增加了对照 CD4(+) T 细胞中 p-STAT2 的表达。与对照者相比，抗 IL-10 抗体能够将 IFN-α 对 IL-17 的抑制作用中和 35%。
体外实验表明，IFN-α 可以抑制 PBMCs 和 CD4(+) T 细胞中 IL-17 的表达并增加 IL-10 的产生。IFN-α 对 IL-17 的抑制作用部分由 IL-10 介导。IFN-α 活性通过 STAT2 磷酸化介导。
