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Plasma Levels of Interleukin-18 and Interleukin-18 Binding Protein Are Elevated in Patients with Chronic Liver Disease

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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.

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Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Innsbruck, Austria

    Othmar Ludwiczek, Arthur Kaser, Wolfgang Vogel & Herbert Tilg

  2. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

    Daniela Novick & Menachem Rubinstein

  3. University of Colorado Health Sciences Center, Denver, Colorado, USA

    Charles A. Dinarello

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  1. Othmar Ludwiczek
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  2. Arthur Kaser
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  4. Charles A. Dinarello
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  6. Wolfgang Vogel
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  7. Herbert Tilg
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Ludwiczek, O., Kaser, A., Novick, D. et al. Plasma Levels of Interleukin-18 and Interleukin-18 Binding Protein Are Elevated in Patients with Chronic Liver Disease. J Clin Immunol 22, 331–337 (2002). https://doi.org/10.1023/A:1020600230977

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