Interferon-α induces interieukin-18 binding protein in chronic hepatitis C patients

Interleukin-18 (IL-18), derived from macrophages and Kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. IL-18 binding protein (IL-18BP) is a circulating protein that binds IL-18 and neutralizes its activity. Since IL-18 production is increased in chronic HCV infection, we asked whether IFN-alpha might act on the IL-18/IL-18BP system in HCV patients. IL-18BP, total and free IL-18 plasma levels were determined in 13 HCV patients receiving 1 x 10(7) IU IFN-alpha subcutaneously daily for 28 days. The in vitro effects of IFN-alpha on macrophage IL-18BP and IL-18 were studied by enzyme-linked immunosorbent assays and Northern analysis. IFN-alpha administration increased IL-18BP plasma levels 3.24 fold 24 h after institution of therapy, resulting in a 67.4% reduction of free IL-18. Total IL-18 levels decreased from day +24 on. In vitro, IFN-alpha diminished IL-18 release from macrophages of healthy volunteers and chronic HCV patients. On top of its inhibitory effects on IL-1 and TNF-alpha release, IFN-alpha also exerts its anti-inflammatory action in vivo by induction of IL-18BP These anti-inflammatory properties might account - together with its antiviral action - for its clinical efficacy in chronic hepatitis C.