Open Access

ARTICLE

Elevated systemic levels of free interleukin-18 (IL-18) in patients with Crohn’s disease

Othmar Ludwiczek¹, Arthur Kaser¹, Daniela Novick², Charles A. Dinarello³, Menachem Rubinstein², Herbert Tilg^1,4

1 University Hospital Innsbruck, Department of Medicine, Division of Gastroenterology and Hepatology, Innsbruck, Austria
2 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
3 University of Colorado Health Sciences Center, Denver, Colorado
4 Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria

* Corresponding Author: H. Tilg,

European Cytokine Network 2005, 16(1), 27-33.

Abstract

Objectives. Interleukin 18 (IL-18) is a proinflammatory cytokine and a member of the IL-1 family. Animal models and investigations in humans point to an important role for this cytokine in inflammatory bowel diseases (IBD). IL-18 binding protein (IL-18BP) is a naturally occurring antagonist of IL-18. Methods. In this study, we measured IL-18 and IL-18BP plasma concentrations and spontaneous release in cultures of colonic explants from healthy subjects (n = 41), patients with Crohn’s disease (CD, n = 135), and patients with ulcerative colitis (UC, n = 93). Results. Both CD and UC patients had higher IL-18BP plasma levels than controls. Plasma levels of free, unbound IL-18 were significantly elevated in CD patients compared to healthy controls, but not in UC patients. Colonic explant cultures from inflamed areas in IBD patients released significantly higher levels of IL-18 than non-inflamed areas and controls. IL-18BP levels from the same cultures were below the detection limit over a culture period of 24 h. Conclusions. Our results confirm the importance of IL-18 in the pathogenesis of IBD and suggest that especially in CD, IL-18BP might be produced in insufficient quantities to counteract the effects of endogenous IL-18.

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