What is disrupting IFN-αʹs antiviral activity? Original Research Article

Despite advances in treatment strategies for hepatitis C virus (HCV), a significant proportion of patients fail to achieve viral clearance following treatment with pegylated interferon (IFN)-α plus ribavirin. Many of these individuals show elevated levels of tumor necrosis factor (TNF)-α compared with normal controls, and recent data have implicated this cytokine in the negative regulation of IFN-α. Although a therapeutic opportunity for TNF-α antagonists might exist for reducing inflammation in chronic HCV disease, further exploration is required to identify the key mediators of responsiveness to IFN-α. In particular, the interplay should be clarified between host response factors [e.g. IFN-α, IFN-γ, suppressor of cytokine signaling (SOCS), TNF-α and others] and pathogen-associated molecular patterns [PAMPs, e.g. lipopolysaccharide (LPS) and CpG DNA] in HCV disease; this information might guide future therapies aimed at improving IFN-α responsiveness.