Blockade of endogenous IL-18 ameliorates TNBS-induced colitis by decreasing local TNF-α production in mice
2001; Elsevier BV; Volume: 121; Issue: 6 Linguagem: Inglês
10.1053/gast.2001.29579
ISSN1528-0012
AutoresTessa ten Hove, Anne Corbaz, Hagit Amitai, Shuki Aloni, Ilana Belzer, Pierre Graber, Paul Drillenburg, Sander J. H. van Deventer, Yolande Chvatchko, Anje A. te Velde,
Tópico(s)Systemic Lupus Erythematosus Research
ResumoBackground & 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) α and IL-1β. IL-18 is up-regulated in colonic specimens of patients with Crohn's disease. The goal of this study was to evaluate the role of IL-18. Methods: Activity of IL-18 was neutralized using recombinant human IL-18 binding protein isoform a (rhIL-18BPa) in trinitrobenzene sulfonic acid (TNBS)–induced colitis. Results: Mice treated daily with rhIL-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-α, IL-6, and IL-1β after rhIL-18BPa treatment but no effect on interferon γ. 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 rhIL-18BPa, may be beneficial for the treatment of IBD.GASTROENTEROLOGY 2001;121:1372-1379
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