Analysis of interleukin-18, interleukin converting enzyme (ICE) and interleukin-18-related cytokines in Crohn's disease lesions

A local increase of interleukin-18 (IL-18) expression has been recently dem onstrated in Crohn's disease (CD), suggesting a role for mature IL-18 (clea ved by ICE protease) in the induction of proinflammatory cytokines and Th1 polarization observed in CD lesions. The aim of this study was to investiga te IL-18 modulation and its potential immune consequences in CD lesions. We showed increased IL-18 production in chronic CD lesions and identified epi thelial cells and macrophages as IL-18-producing cells. A twofold increase in ICE alpha, beta, and/or gamma mRNA that encodes for the complete mature peptide required for ICE activity, and a marked increase in IL-18R-positive immune cells was observed in chronic lesions compared to uninvolved areas or normal control samples. Chronic lesions also displayed intense transcrip tion of IL-18-induced cytokines, IFN-gamma, IL-1 beta, TNF-alpha, and IL-8, By contrast, when neither IL-18 nor ICE mRNAs were enhanced (early asympto matic CD lesions), IL-18-induced cytokines were not up-regulated. These res ults are in accordance with a putative role of mature IL-18 in the pathogen esis of CD,