Evidence for Mast Cell Activation in Patients with Therapy-Resistant Irritable Bowel Syndrome

Zusammenfassung

Neuere Untersuchungen legen eine wesentliche Rolle von Mastzellen in der Pathogenese des Reizdarmsyndroms nahe. Ziel der vorliegenden Pilotstudie war es, die mögliche pathophysiologische Rolle von Mastzellen in Reizdarmpatienten mit einem neuartigen Untersuchungsansatz näher zu beleuchten. An 20 Patienten mit therapierefraktärem Reizdarmsyndrom wurde mit einer validierten Checkliste, die die Identifizierung von Mastzellmediator-vermittelten Symptomen erlaubt, und mit ausgesuchten Surrogatparametern das Vorliegen einer pathologisch gesteigerten Aktivität von Mastzellen mit gesteigerter Mediatorfreisetzung untersucht. Bei 19 der 20 untersuchten Patienten konnten Mastzellmediator-induzierte Symptome festgestellt werden. In Abhängigkeit von der Mastzellaktivität pathologisch veränderte Koagulation- und Finbrinolyseparameter wurden bei 11 von 12 dahingehend untersuchten Patienten gefunden. Ein weiterer Patient hatte einen pathologisch erhöhten Methylhistamingehalt im Urin. Die vorliegenden Befunde geben einen Hinweis auf eine hohe Prävalenz für eine pathologisch gesteigerte systemische Mastzellaktivität bei Patienten mit einem therapierefraktärem Reizdarmsyndrom. Diese Beobachtung passt zu der Vorstellung, dass aktivierte Mastzellen in die Pathophysiologie des Reizdarmsyndroms eingebunden sind. Reizdarmpatienten mit therapierefraktärer Symptomatik könnten demnach therapeutisch von der Gabe mastzellstabilisierender Medikamente oder von Wirkstoffen, die die Mediatorwirkung an den Erfolgsorganen antagonisieren, profitieren.

Abstract

Previous findings suggested an involvement of mast cells in the pathogenesis of irritable bowel syndrome (IBS). The pathophysiological significance of mast cells is defined both by their number in tissue and by their activity. In the present pilot study activity of mast cells in patients with therapy-resistant IBS was investigated for the first time systematically. Twenty patients with therapy-resistant IBS were investigated for the presence of a pathologically increased mast cell mediator release by means of a validated structured interview suitable to identify mast cell mediator-related symptoms and by determing selected surrogate parameters for mast cell activity. Nineteen of the 20 patients presented mast cell mediator-related symptoms. Pathologically increased mast cell activity-related coagulation and fibrinolysis parameters were detected in 11 of 12 patients investigated in that regard. One patient had an elevated level of methylhistamine in urine. The present data provide evidence that in patients with therapy-resistant IBS a pathologically increased systemic mast cell activity may occur with high prevalence. This finding fits to the idea of an assumed contribution of activated mast cells in the pathophysiology of IBS.

Schlüsselwörter

Colon irritabile - Reizdarm - Mastzellen - Mastzellmediator-vermittelte Symptome - c-kit

Key words

irritable bowel syndrome - IBS - mast cell - c-kit - mast cell mediator release syndrome

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