IFN-α blocks IL-17 production by peripheral blood mononuclear cells in Behçet's disease

Objectives. IFN-a has been used to treat patients with Behcet'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-a could affect this pathway. Methods. Peripheral blood mononuclear cells (PBMCs) obtained from patients with active BD and controls were cultured alone or with IFN-a 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-a were also evaluated by ELISA. Furthermore, an experiment using anti-IL-10 was performed to examine underlying mechanisms of action of IFN-a. Results. Significantly higher levels of IL-17 and IL-10 were observed in the supernatants of PBMCs from BD patients as compared with controls. IFN-a significantly decreased IL-17 production by PBMCs from both patients and controls. On the other hand, IFN-a increased IL-10 production by PBMCs from patients and controls. Similar findings were obtained when using CD4 + T cells from controls, IFN-a significantly increased p-STAT2 expression in control CD4 + T cells. Anti-IL-10 antibody was able to neutralize the inhibitory effect of IFN-a on IL-17 by 35% as compared with controls. Conclusions. In vitro experiments showed that IFN-a could inhibit IL-17 expression and increased IL-10 production by PBMCs and CD4 + T cells. The inhibitory role of IFN-a on IL-17 was partly mediated by IL-10. IFN-a activity was mediated via STAT2 phosphorylation.