IFN-alpha blocks IL-17 production by peripheral blood mononuclear cells in Behcet's disease.
OBJECTIVE
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.


METHODS
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.


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-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.


CONCLUSIONS
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.
Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Xiaoli
X
Liu
Peizeng
P
Yang
Chaokui
C
Wang
Fuzhen
F
Li
Aize
A
Kijlstra
D000328:Adult; D001528:Behcet Syndrome / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male
D016898:Interferon-alpha; D020381:Interleukin-17; D016753:Interleukin-10