IL-18, a Novel Immunoregulatory Cytokine, Is Up-Regulated in Crohn’s Disease: Expression and Localization in Intestinal Mucosal Cells

TLDR

IL‑18 is a novel immunoregulatory cytokine that induces IFN‑γ and may contribute to Th1‑mediated chronic inflammatory disorders. The study aimed to determine the expression levels and cellular localization of IL‑18 in colonic tissues and mucosal cell populations from Crohn’s disease patients. Using semiquantitative RT‑PCR and immunohistochemistry, IL‑18 mRNA and protein were found to be up‑regulated in intestinal epithelial cells and lamina propria mononuclear cells, particularly in macrophages and dendritic cells, in Crohn’s disease versus ulcerative colitis and controls. IL‑18 expression was markedly higher in Crohn’s disease tissues, especially in involved areas, with mature IL‑18 predominating in CD biopsies and the precursor form present only in non‑inflamed controls, highlighting a novel Th1‑mediated inflammatory signature and the immunoregulatory role of epithelial and dendritic cells.

Abstract

Abstract IL-18, a novel immunoregulatory cytokine with potent IFN-γ-inducing activities, may play an important role in Th1-mediated chronic inflammatory disorders. The aim of the present study was to characterize the expression and localization of IL-18 in colonic specimens and isolated mucosal cell populations from patients with Crohn’s disease (CD), a prototypic Th1-mediated disorder. Using a semiquantitative RT-PCR protocol, IL-18 mRNA transcripts were found to be increased in freshly isolated intestinal epithelial cells (IEC) and lamina propria mononuclear cells (LPMC) from CD compared with ulcerative colitis (UC) and noninflamed control (cont) patients, and were more abundant in IEC compared with LPMC. Immunohistochemical analysis of surgically resected colonic tissues localized IL-18 to both LPMC (specifically, macrophages and dendritic cells) as well as IEC. Staining was more intense in CD compared with UC and cont, and in involved (inv) vs noninvolved (n inv) areas. Western blot analysis revealed that an 18.3-kDa band, consistent with both recombinant and mature human IL-18 protein, was found predominantly in CD vs UC intestinal mucosal biopsies; a second band of 24 kDa, consistent with the inactive IL-18 precursor, was detected in n inv areas from both CD and UC biopsies and was the sole form found in noninflamed cont. To our knowledge, this report is the first describing increased expression of IL-18 in a human Th1-mediated chronic inflammatory disease. In addition, our studies further support the concept that IEC and dendritic cells may possess important immunoregulatory functions in both normal, as well as pathological, mucosal immunity.