Therapeutic options in inflammatory bowel disease: Experimental evidence of a beneficial effect of kinin B 1 receptor blockade

Abstract

A surprising proportion of patients with inflammatory bowel disease (IBD) remain refractory to all classes of drugs presently in clinical use. Kinins are inflammatory mediators of potential relevance in IBD, because at least the kinin B 1 receptor subtype is upregulated in human or animal intestinal inflammation and also both B 1 and B 2 receptors for kinins support inflammation and epithelial electrogenic ion transport that leads to secretory diarrhoea. In this issue of the BJP, Hara et al. report the therapeutic effect of a modern and selective nonpeptide kinin B 1 receptor antagonist, SSR240612 ((2R)-2-(((3R)-3-(1,3-benzodioxol-5-yl)-3-(((6- methoxy-2-naphthyl)sulphonyl)amino)propanoyl)amino)-3-(4-((2R,6S)-2, 6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide hydrochloride), with benefits such as decreased neutrophil influx and improved macroscopic tissue scoring. The results were corroborated using kinin B 1 receptor gene-knockout mice. Further, kinin B 1 receptor upregulation in this inflammatory model is partially dependent on TNF-α, a recognized target for IBD pharmacotherapy. More work is warranted to evaluate the value of the kinin B 1 receptor antagonists as a novel anti-inflammatory therapeutic option for IBD. © 2008 Nature Publishing Group All rights reserved.