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Blockade of endogenous IL-18 ameliorates TNBS-induced colitis by decreasing local TNF-@a. Production in mice

Authors :
Ten Hove, T.
Corbaz, A.
Amitai, H.
Aloni, S.
Belzer, I.
Graber, P.
Drillenburg, P.
Van Deventer, S.J.H.
Chvatchko, Y.
Te Velde, A.A.
Source :
Gastroenterology; December 2001, Vol. 121 Issue: 6 p1372-1379, 8p
Publication Year :
2001

Abstract

Background & Aims:: Interleukin (IL) 18 has proinflammatory effects. IL-18 plays a pivotal role in Th1 responses, but its proinflammatory activities extend beyond Th1 cells, including macrophages and production of tumor necrosis factor (TNF) @a and IL-1@b. 1L-48 is up-regulated in colonic specimens of patients with Crohn's disease. The goal of this study was to evaluate the role of 11-48. Methods:: Activity of IL-18 was neutralized using recombinant human IL-48 binding protein isoform a (rhlL-18BPa) in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Results:: Mice treated daily with rhlL-18BPa (8 mg/kg) had significant reductions in clinical score, body weight loss, and colon weight increase compared with saline-treated mice. Histologic analysis showed that rhIL-18BPa-treated mice developed only mild colitis without signs of ulceration, with a mean total score of 9.8 +/- 1.3 points compared with 15.9 +/- 1.1 points observed in saline-treated mice with colitis. Analysis of cytokine levels in colon homogenates showed a significant decrease in TNF-@a, IL-6, and IL-1@b after rhIL-18BPa treatment but no effect on interferon @c. The therapeutic potential of rhIL-18BPa treatment was confirmed in TNBS mice that were treated only on days 8 and 9 after the start of the experiment. In these mice, significant reductions in total colitis score and colon weight were also observed. Conclusions:: These findings show that inhibition of rhIL-18BPa bioactivity, via rhlL-18BPa, may be beneficial for the treatment of IBD.

Details

Language :
English
ISSN :
00165085 and 15280012
Volume :
121
Issue :
6
Database :
Supplemental Index
Journal :
Gastroenterology
Publication Type :
Periodical
Accession number :
ejs11055899
Full Text :
https://doi.org/10.1053/gast.2001.29579