title: Plasma levels of interleukin-18 and interleukin-18 binding protein are elevated in patients with chronic liver disease.
abstract: Interleukin 18 (IL-18) is a recently described proinflammatory cytokine. In mouse models it has been shown to play a key role in the development of liver injury. IL-18 binding protein (IL-18BP) is a naturally occurring antagonist of IL-18. In this study we investigated whether IL-18/IL-18BP levels are altered in patients with chronic liver disease (CLD). We measured IL-18 and IL-18BP plasma levels in 153 patients with CLD and 41 healthy controls by a specific ELISA. Plasma levels of IL-18 were significantly higher in CLD patients than in healthy controls. Cirrhotics had higher levels than noncirrhotics. IL-18 levels increased with disease progression. IL-18BP plasma levels paralled the increase of IL-18 with disease progression, except in stage Child C cirrhosis. IL-18 and IL-18BP levels were elevated independent of the etiology of CLD. IL-18 and IL-18BP correlated with laboratory parameters of inflammation and liver injury. Plasma levels of IL-18 and its antagonist, IL-18BP, are elevated in CLD and correlate with severity of disease. IL-18BP may not be sufficient to counteract the overwhelming proinflammatory response in end stage liver disease.
authors.affiliation: University Hospital Innsbruck, Department of Medicine, Division of Gastroenterology and Hepatology, Innsbruck, Austria.
authors.forename: Othmar
authors.initials: O
authors.lastname: Ludwiczek
authors.forename: Arthur
authors.initials: A
authors.lastname: Kaser
authors.forename: Daniela
authors.initials: D
authors.lastname: Novick
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Menachem
authors.initials: M
authors.lastname: Rubinstein
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vogel
authors.forename: Herbert
authors.initials: H
authors.lastname: Tilg
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000097:blood / Q000276:immunology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology*; D008107:Liver Diseases / Q000097:blood / Q000276:immunology*; D008875:Middle Aged
chemical_list: D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; C118370:interleukin-18 binding protein