BACKGROUND: Interleukin-18 (IL-18) is increased in the inflamed mucosa of patients with Crohn's disease (CD). The balance between this pleiotropic proinflammatory cytokine and its natural inhibitor, IL-18-binding protein (IL-18BP), may contribute to the pathogenesis of inflammatory bowel disease (IBD). METHODS: Serum and mucosal biopsies were collected from children with IBD, from children with celiac disease, and from controls. Biopsies were maintained in culture for 24 hours, and supernatant was collected. Serum and supernatant IL-18 and IL-18BPa concentrations were measured by immunoassay. Disease activity score (PCDAI) and standard serum inflammatory markers (albumin, platelets, ESR, and CRP) were recorded. RESULTS: Serum IL-18 was greater in children with CD (537 pg/mL) than in controls (335 pg/mL; P < 0.05) but not in children with ulcerative colitis (UC) or IBD type unclassified (IBDU). Mucosal IL-18 was greater in children with CD and UC/IBDU than in controls (P < 0.01). Serum IL-18BPa was increased in children with CD compared with that in controls (3.9 versus 2.6 ng/mL; P < 0.05), but was not elevated in children with UC/IBDU. Furthermore, calculated free-serum IL-18 was elevated in CD, but not UC/IBDU, compared with that in controls (P = 0.001). Total and free-serum IL-18 were elevated in severe CD relative to in mild/moderate disease. CONCLUSIONS: IL-18, produced in the colons of children with IBD, may contribute to local inflammatory changes. Systemic IL-18 level may be a useful indicator of gut inflammation. Furthermore, free IL-18 is greatly elevated in children with CD, suggesting that compensatory increases in IL-18BPa are insufficient. Further exploration of the role of this cytokine in the pathogenesis of IBD is now required.
BACKGROUND:Interleukin-18 (IL-18) is increased in the inflamed mucosa of patients with Crohn's disease (CD). The balance between this pleiotropic proinflammatory cytokine and its natural inhibitor, IL-18-binding protein (IL-18BP), may contribute to the pathogenesis of inflammatory bowel disease (IBD). METHODS: Serum and mucosal biopsies were collected from children with IBD, from children with celiac disease, and from controls. Biopsies were maintained in culture for 24 hours, and supernatant was collected. Serum and supernatant IL-18 and IL-18BPa concentrations were measured by immunoassay. Disease activity score (PCDAI) and standard serum inflammatory markers (albumin, platelets, ESR, and CRP) were recorded. RESULTS: Serum IL-18 was greater in children with CD (537 pg/mL) than in controls (335 pg/mL; P < 0.05) but not in children with ulcerative colitis (UC) or IBD type unclassified (IBDU). Mucosal IL-18 was greater in children with CD and UC/IBDU than in controls (P < 0.01). Serum IL-18BPa was increased in children with CD compared with that in controls (3.9 versus 2.6 ng/mL; P < 0.05), but was not elevated in children with UC/IBDU. Furthermore, calculated free-serum IL-18 was elevated in CD, but not UC/IBDU, compared with that in controls (P = 0.001). Total and free-serum IL-18 were elevated in severe CD relative to in mild/moderate disease. CONCLUSIONS:IL-18, produced in the colons of children with IBD, may contribute to local inflammatory changes. Systemic IL-18 level may be a useful indicator of gut inflammation. Furthermore, free IL-18 is greatly elevated in children with CD, suggesting that compensatory increases in IL-18BPa are insufficient. Further exploration of the role of this cytokine in the pathogenesis of IBD is now required.
Authors: Tere M Williams; Rachel A Leeth; Daniel E Rothschild; Sheryl L Coutermarsh-Ott; Dylan K McDaniel; Alysha E Simmons; Bettina Heid; Thomas E Cecere; Irving C Allen Journal: J Immunol Date: 2015-02-27 Impact factor: 5.422
Authors: Kirk Bergstrom; Xiaowei Liu; Yiming Zhao; Nan Gao; Qian Wu; Kai Song; Yi Cui; Yun Li; J Michael McDaniel; Samuel McGee; Weichang Chen; Mark M Huycke; Courtney W Houchen; Lauren A Zenewicz; Christopher M West; Hong Chen; Jonathan Braun; Jianxin Fu; Lijun Xia Journal: Gastroenterology Date: 2016-04-06 Impact factor: 22.682
Authors: R C P Lima-Júnior; H C Freitas; D V T Wong; C W S Wanderley; L G Nunes; L L Leite; S P Miranda; M H L P Souza; G A C Brito; P J C Magalhães; M M Teixeira; F Q Cunha; R A Ribeiro Journal: Br J Pharmacol Date: 2014-05 Impact factor: 8.739
Authors: Nina A Mikirova; James A Jackson; Ron Hunninghake; Julian Kenyon; Kyle W H Chan; Cathy A Swindlehurst; Boris Minev; Amit N Patel; Michael P Murphy; Leonard Smith; Doru T Alexandrescu; Thomas E Ichim; Neil H Riordan Journal: J Transl Med Date: 2009-12-15 Impact factor: 5.531