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


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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@article{Ludwiczek2005ElevatedSL, title={Elevated systemic levels of free interleukin-18 (IL-18) in patients with Crohn's disease.}, author={Othmar Ludwiczek and Arthur Kaser and Daniela Novick and Charles Anthony Dinarello and Menachem Rubinstein and Herbert Tilg}, journal={European cytokine network}, year={2005}, volume={16 1}, pages={27-33} }