Interleukin 6 (IL-6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells, including hepatocytes. Previous studies have shown that serum IL-6 levels are increased in hepatitis B patients. However, the role of IL-6 in modulating the anti-hepatitis B virus (HBV) activity of interferon-α (IFN-α) remains unclear. In this study, we found that both HBV and viral proteins could induce the expression of IL-6 in hepatocytes (LO2 and HepG2). Exogenous IL-6 had no effect on HBV replication, whereas knockdown of IL-6 expression by RNAi inhibited that. Interestingly, IFN-α markedly induced IL-6 expression in hepatocytes, especially in HBV replicating hepatocytes. In turn, IL-6 impaired the anti-HBV efficiency of IFN-α by decreases the expression of IFN-α downstream effectors by upregulation of suppressor of cytokine signaling-3 (SOCS3). Furthermore, we demonstrated that downregulation of SOCS3 improved IFN antiviral activity to some extent in HBV replicating hepatocytes. These data provided new insights for a better understanding of the mechanism of IFN-α resistance and may represent a novel therapeutic strategy to efficiently target HBV infection.
Keywords: hepatitis B virus; interferon-α; interleukin 6; suppressor of cytokine signaling-3.
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