Interferon-alpha induces interleukin-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 107 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.
Kaser
A
A
Division of Gastroenterology and Hepatology, Department of Medicine, University Hospital Innsbruck, Innsbruck, Austria.
Novick
D
D
Rubinstein
M
M
Siegmund
B
B
Enrich
B
B
Koch
R O
RO
Vogel
W
W
Kim
S H
SH
Dinarello
C A
CA
Tilg
H
H
D015536:Down-Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D020382:Interleukin-18 / Q000096:biosynthesis / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D020382:Interleukin-18; D012333:RNA, Messenger; D011994:Recombinant Proteins; C118370:interleukin-18 binding protein