IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: Expression and localization in intestinal mucosal cells

Theresa T. Pizarro*, Miette H. Michie, Marcia Bentz, Jan Woraratanadharm, Michael F. Smith, Eugene Foley, Christopher A. Moskaluk, Stephen J. Bickston, Fabio Cominelli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

527 Scopus citations

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.

Original languageEnglish
Pages (from-to)6829-6835
Number of pages7
JournalJournal of Immunology
Volume162
Issue number11
StatePublished - 1 Jun 1999
Externally publishedYes

Fingerprint

Dive into the research topics of 'IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn's disease: Expression and localization in intestinal mucosal cells'. Together they form a unique fingerprint.

Cite this