Irritable Bowel Syndrome: Diagnosis and Clinical Management by Anton Emmanuel

Author:Anton Emmanuel
Language: eng
Format: mobi, pdf
Publisher: Wiley
Published: 2013-04-09T21:00:00+00:00

Potential anti-inflammatory agents for IBS

Aminosalicylates

5-Aminosalicylic acid (mesalazine) is an anti-inflammatory agent widely used in the treatment of ulcerative colitis and Crohn’s disease. Three preliminary uncontrolled trials had suggested that mesalazine could reduce pain and stool frequency, and improve stool consistency in patients with post-infectious and nonspecific IBS [85, 86]. In a small randomized, double-blind, placebo-controlled trial, Corinaldesi et al. tested the efficacy of mesalazine (800 mg three times daily for eight weeks) on intestinal immune cells and symptom perception in a mixed group of twenty IBS patients [87]. A significant improvement in general well-being was observed, with a trend for improvement in abdominal pain and frequency of bowel movement. No serious adverse drug reactions were observed. Given the small sample size and the pilot nature of the study, further studies are required to confirm the efficacy of mesalazine on IBS symptoms. Nonetheless, this study is particularly encouraging because mesalazine treatment was associated with markedly reduced mucosal immune cells and, in particular, mast cells, suggesting that mesalazine acted through an immune-mediated anti-inflammatory effect in this group of IBS patients. Barbara et al. have also proposed other actions of mesalazine that could operate in IBS patients with an inflammatory underpinning: alterations in the gut flora, modulation of protease release and enhancement of epithelial barrier function [41, 85, 88, 89].

Mast cell stabilisers

Barbara et al. had shown in 2004 [36] that activated mast cells were present in close proximity to colonic neurons and that the density correlated with the severity of abdominal pain reported by the IBS patients. The therapeutic potential of agents with activity on mast cells has been reviewed [89]. Chromones (e.g. cromolyn sodium, nedocromil sodium) are compounds that act primarily by stabilizing the plasma membrane of mast cells, controlling the release of mast cell mediators such as histamine. In the 1980s, disodium cromoglycate was tested in twenty IBS patients with diarrhoea and observed to have a 40% therapeutic advantage over placebo in improving symptom scores [90]. The benefit appeared to be independent of the presence of atopy, food intolerance or lactase deficiency. On the other hand, in another small double-blind, placebo-controlled study, sodium cromoglycate significantly improved abdominal pain and diarrhoea in patients with IBS-D who also reported food intolerance [91]. Similarly, two uncontrolled, unblinded studies comparing oral cromoglycate against elimination diet therapy in patients with IBS-D reported high response rates of over 60% with both treatments; in both treatment arms it was suggested that patients with positive skin tests for dietary antigens were more likely to respond favourably [92, 93]. Two other unblinded studies which purported that cromoglycate improved symptoms in IBS-D patients provided some mechanistic insights by suggesting effects via enhancement of mucosal barrier function and reduction in mucosal tryptase release [94, 95]. One potential limitation to the role of cromoglycate is that in many countries it is available only as an inhaler for the treatment of asthma; the reason is that cromoglycate is not amenable to absorption when ingested orally, although this actually makes it an excellent compound for targeting mast cells in the gastrointestinal mucosa, without incurring systemic side effects.

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