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