Bioactive IL-18 expression is up-regulated in Crohn's disease

An imbalance of immunoregulatory factors is believed to contribute to uncon trolled mucosal Th1 cell activation in Crohn's disease (CD), IL-18, a macro phage-like cell-derived cytokine, is involved in Th1 clone development, and IFN-gamma production. Therefore, IL-18 expression was investigated in CD, Whole mucosal intestinal tissue and lamina propria mononuclear cells (LPMC) of 12 CD and 9 ulcerative colitis (UC) patients and 15 non-inflammatory bo wel disease (IBD) controls were tested for IL-18 by semiquantitative RT-PCR and Western blot analysis, Transcripts for IL-18 were found in all samples tested. However, increased IL-18 mRNA accumulation was detected in both mu cosal and LPMC samples from CD in comparison to UC and controls. In CD, tra nscripts for IL-18 were more abundant in the mucosal samples taken from inv olved areas, An 18-kDa band consistent with mature IL-18 was predominantly found in CD mucosal samples, In mucosal samples from non-IBD controls, IL-1 8 was present as a 24-kDa polypeptide, Consistently, active IL-1 beta-conve rting enzyme (ICE) subunit (p20) was expressed in samples from either CD or UC, whereas, in colonic mucosa from non-IBD controls, ICE was synthesized as precursor (p45) only, To confirm that IL-18 produced in CD tissue was fu nctionally active, CD LPMC were treated with a specific IL-18 antisense oli gonucleotide. In these cultures, IL-18 down-regulation was accompanied by a decrease in IFN-gamma expression, In aggregate, our data indicate that IL- 18 up-regulation is a feature of CD and suggest that IL-18 may contribute t o the local immunoinflammatory response in CD.