The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome

Klooker, Tamira K.; Braak, Breg; Koopman, Karin E.; Welting, Olaf; Wouters, Mira M.; Heide, S. van der; Schemann, Michael; Bischoff, Stephan C.; Wijngaard, René M. van den; Boeckxstaens, Guy E.

doi:10.1136/gut.2010.213108

Cited by 352 publications

(332 citation statements)

References 40 publications

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“…5 Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients in several studies, and partially exhibited good efficacy in symptom improvement. 6,7 It further supported the key role of MCs in the process of IBS. In this review, it discussed the mechanisms of MCs in the gut dysfunctions of IBS.…”

Section: Introductionmentioning

confidence: 72%

“…6 A placebocontrolled trail in 60 IBS patients showed that 8 weeks of treatment with ketotifen obviously increased the threshold for discomfort in IBS patients with visceral hypersensitivity, reduced IBS symptoms, and improved the health-related quality of life. 7 Furthermore, a prior study of 120 D-IBS patients with one or more food intolerance indicated that dietary exclusion along with oral DSCG was effective in these patients, and had a prolonged symptomatic benefit. 6 However, these studies had several limitations, such as poor design, small sample size, and selection bias.…”

Section: Mast Cells As Potential Therapeutic Target For Irritable Bowmentioning

confidence: 99%

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Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

110

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Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder since it lacks demonstrable pathological abnormalities. However, in recent years, low grade inflammatory infiltration, often rich in mast cells, in both the small and large bowel, has been observed in some patients with IBS. The close association of mast cells with major intestinal functions, such as epithelial secretion and permeability, neuroimmune interactions, visceral sensation, and peristalsis, makes researchers and gastroenterologists to focus attention on the key roles of mast cells in the pathogenesis of IBS. Numerous studies have been carried out to identify the mechanisms in the development, infiltration, activation, and degranulation of intestinal mast cells, as well as the actions of mast cells in the processes of mucosal barrier disruption, mucosal immune dysregulation, visceral hypersensitivity, dysmotility, and local and central stress in IBS. Moreover, therapies targeting mast cells, such as mast cell stabilizers (cromoglycate and ketotifen) and antagonists of histamine and serotonin receptors, have been tried in IBS patients, and have partially exhibited considerable efficacy. This review focuses on recent advances in the role of mast cells in IBS, with particular emphasis on bridging experimental data with clinical therapeutics for IBS patients.

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Section: Introductionmentioning

confidence: 72%

Section: Mast Cells As Potential Therapeutic Target For Irritable Bowmentioning

confidence: 99%

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Zhang

Song

Hou

2016

J Neurogastroenterol Motil

110

View full text Add to dashboard Cite

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“…Ketotifen, a mast cell stabilizer and an H1 receptor antagonist, improved IBS symptoms and quality of life [37]. This study performed in human reinforced the possibility of the use of mast cell stabilizers as a therapeutic approach in the treatment of patients with IBS [37].…”

Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 88%

“…These supernatants were characterized by an increase in tryptase, histamine and PGE 2 concentration compared to healthy control [36]. Ketotifen, a mast cell stabilizer and an H1 receptor antagonist, improved IBS symptoms and quality of life [37]. This study performed in human reinforced the possibility of the use of mast cell stabilizers as a therapeutic approach in the treatment of patients with IBS [37].…”

Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 99%

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Cenac

2013

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Abstract:The protease-activated receptors (PARs) play a pivotal role in inflammatory and nociceptive processes. PARs have raised considerable interest because of their capacity to regulate numerous aspects of viscera physiology and pathophysiology. The present article summarizes research on PARs and proteases as signalling molecules in visceral pain. In particular, experiments in animal models suggest that PAR 2 is important for visceral hypersensitivity. Moreover, endogenous PAR 2 agonists seem to be released by colonic tissue of patients suffering from irritable bowel syndrome, suggesting a role for this receptor in visceral pain perception. Thus, PARs, together with proteases that activate them, represent exciting targets for therapeutic intervention on visceral pain.

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“…Th ey also suggest that cysteine as well as serine proteases may be involved in this process -an interesting fi nding given the presence of cysteine proteases in intestinal cells other than mast cells, the dominant source of serine proteases. Th e role of mast cells in IBS has been the subject of considerable interest and, although some have reported increased mast cell numbers and / or activation in IBS ( 22 -25 ), this fi nding has not been universal ( 26,27 ). Th e observation that proteases other than those derived from mast cells could be involved in neuronal eff ects mediated by IBS supernatants is an important one but the possibility that these proteases could be of bacterial origin also needs to be considered ( 28 ).…”

mentioning

confidence: 99%

Editorial: PARs for the Course: Roles of Proteases and PAR Receptors in Subtly Inflamed Irritable Bowel Syndrome

Quigley

2013

American Journal of Gastroenterology

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Although the etiology of irritable bowel syndrome (IBS) remains unknown, clinical and laboratory observations suggest that within the broad and varying phenotype, that is, IBS, there may exist subgroups, which can be defi ned on the basis of a distinctive pathophysiological basis. Of these, postinfectious IBS is the best characterized; in IBS, in general, studies of infl ammatory mediators and substances elaborated by cells involved in the intestinal immune response, such as proteases, suggest that some IBS sufferers can be differentiated on the basis of an aberrant immune response. Valdez-Morales and colleagues extend this concept by demonstrating the ability of supernatants of biopsy cultures from individuals with diarrheapredominant IBS to enhance neuronal excitabilityan effect that could well contribute to a clinical hallmark of IBS, namely, visceral hypersensitivity. Am J Gastroenterol 2013; 108:1644 -1646 doi: 10.1038/ajg.2013 Irritable bowel syndrome (IBS) is a common and, at times, disabling condition whose etiology, despite the best eff orts of clinicians and scientists, remains unclear. As a consequence, reliable biomarkers for the syndrome have yet to emerge, and its diagnosis, therefore, continues to rest on clinical features and the exclusion of disorders that have the potential to present in a similar manner ( 1 ). Much of the diffi culties related to unraveling the enigma that is IBS revolve around its heterogeneity, which may originate from any one or a combination of the following: dominant symptom (pain, discomfort, bloating, distension, and altered bowel habit), predominant bowel habit (diarrhea, constipation, or mixed pattern), comorbidity (be it psychological or somatic), severity (including impact on the quality of life), natural history, and prognosis. To frustrate the clinician scientist further, those IBS subtypes that can be defi ned with some degree of accuracy, at least using Rome III criteria (2), including diarrhea-predominant IBS, constipationpredominant IBS and mixed IBS, do not appear to be immutable, and suff erers can move from one stool pattern to another over time, thus emphasizing the importance of longitudinal studies of this disorder ( 3,4 ).However, in this rather gloomy scenario, shines an unexpected beam of light that has illuminated (or, to be accurate, reignited) a new perspective on the etiology of IBS -postinfectious IBS (PI-IBS) ( 5 ). Although PI-IBS had been well described decades beforehand ( 6 ), more recent studies based on the consequences of large-scale outbreaks of bacterial, viral, and amebic gastroenteritis have firmly brought the concept of host -microbiome interactions into play in IBS research, in general ( 7 ). Observations in relation to PI-IBS, such as the description of correlations between the initial inflammatory response to the infection and the subsequent development of IBS ( 8 ), as well as the identification of polymorphisms in genes coding for components of the mucosal immune response and intestinal barrier integrity as risk factor...

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The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome

Cited by 352 publications

References 40 publications

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Editorial: PARs for the Course: Roles of Proteases and PAR Receptors in Subtly Inflamed Irritable Bowel Syndrome

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