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.
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 CDpatients compared to healthy controls, but not in UC patients. Colonic explant cultures from inflamed areas in IBDpatients 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.
Authors: C Schmidt; T Giese; R Goebel; M Schilling; T Marth; A Ruether; S Schreiber; S Zeuzem; S C Meuer; A Stallmach Journal: Int J Colorectal Dis Date: 2007-02-21 Impact factor: 2.571
Authors: Michael Thiele; Randolf J Kerschbaumer; Frederick W K Tam; Dirk Völkel; Patrice Douillard; Alexander Schinagl; Harald Kühnel; Jennifer Smith; John P McDaid; Gurjeet Bhangal; Mei-Ching Yu; Charles D Pusey; H Terence Cook; Josef Kovarik; Erica Magelky; Atul Bhan; Manfred Rieger; Geert C Mudde; Hartmut Ehrlich; Bernd Jilma; Herbert Tilg; Alexander Moschen; Cox Terhorst; Friedrich Scheiflinger Journal: J Immunol Date: 2015-07-24 Impact factor: 5.422