Abstract
BackgroundIFN-α has been used to treat patients with chronic active hepatitis B (CAHB). Recent studies have implicated the IL-23/Th-17 pathway in the pathogenesis of CAHB. In this study, we investigated whether IFN-α could affect this pathway.MethodsPeripheral blood mononuclear cells (PBMCs) obtained from patients with active CAHB (n = 61) and controls (n = 32) were cultured with or without IFN-α, and the levels of IL-17 and IL-10 in the supernatants were determined by ELISA, while the frequency of IL-17-expressing cells was measured by FACS. Similar experiments were also conducted with isolated CD4+ T cells from controls. Furthermore, an experiment using an anti-IL-10 antibody was performed to examine the underlying mechanisms of action of IFN-α.ResultsBoth the levels of IL-17 and the frequency of IL-17-expressing cells were significantly higher in the PBMCs from CAHB patients than in the controls. IFN-α significantly decreased IL-17 production and the frequency of IL-17-expressing cells in PBMCs from both patients and controls. On the other hand, IFN-α increased IL-10 production by PBMCs from patients and controls. Anti-IL-10 antibody was able to neutralize the inhibitory effect of IFN-α on IL-17 production by PBMCs.ConclusionsIn vitro experiments showed that IFN-α could inhibit IL-17 expression and increase IL-10 production by PBMCs and CD4+ T cells. The inhibitory role of IFN-α on IL-17 production was partly mediated by IL-10.
Highlights
IFN-α has been used to treat patients with chronic active hepatitis B (CAHB)
The frequency of IL-17-expressing CD4+ T cells is significantly increased in CAHB patients and addition of rhIFN-α 2a decreases the frequency of IL-17 expressing cells from both patients and controls We further analyzed the frequency of IL-17- expressing T cells in CAHB patients (n = 61) and controls (n = 32) using FACS analysis
CD4-T cells expressed IL-17, but since the frequencies of IL-17-expressing CD4-T cells were extremely low in CAHB patients, we only investigated the CD4+ T cells
Summary
IFN-α has been used to treat patients with chronic active hepatitis B (CAHB). Recent studies have implicated the IL-23/Th-17 pathway in the pathogenesis of CAHB. We investigated whether IFN-α could affect this pathway. Hepatitis B virus (HBV) infection, the major cause of chronic liver injury and inflammation, can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma [1,2]. IFN-α has been used for the treatment of HBV infectionassociated complications with promising results. The mechanisms whereby IFN-α exerts its immunomodulatory effects in HBV-infected patients are, not completely understood. It was suggested that the IL-23/Th-17 pathway is implicated in the pathogenesis of the immune response to promote liver damage [3,4], and that the effective treatment of CAHB patients with IFN-α might be mediated increased IL-10 production by PBMCs from both CAHB patients and controls. We found that the inhibitory role of IFN-α on IL-17 production was partially mediated by IL-10
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