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Z Gastroenterol 2013; 51(4): 384-389
DOI: 10.1055/s-0033-1335042
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Mukosaschutz durch Phosphatidylcholin als neues therapeutisches Prinzip bei der Colitis ulcerosa

Mucosal Protection by Phosphatidylcholine as New Therapeutic Concept in Ulcerative Colitis
W. Stremmel
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Publication History

19 October 2012

30 January 2013

Publication Date:
12 April 2013 (online)

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Zusammenfassung

Die Schleimschicht auf der Kolonmukosa stellt die erste Barriere gegen eine Invasion kommensaler Bakterien im Stuhl dar. Ein essenzieller Bestandteil des intestinalen Mucus ist Phosphatidylcholin (PC), welches mehr als 90 % der Phospholipide im Mucus ausmacht und deshalb als selektive Anreicherung von PC in diesem Kompartiment angesehen wird. Phosphatidylcholin ist in lamellaren Strukturen, ähnlich wie das Surfactant der Lunge, angeordnet und konstituiert somit eine hydrophobe Schicht auf der Oberfläche des wässrigen Mucusgels, um so vor der Invasion von Bakterien aus dem intestinalen Lumen zu schützen. Bei Colitis ulcerosa (UC) ist der PC-Gehalt des Mucus um 70 % vermindert unabhängig davon, ob die Schleimhaut entzündet ist oder nicht. Somit ist der verminderte PC-Gehalt im Mucus eine intrinsische primäre pathogenetische Voraussetzung zur Invasion von Bakterien und Auslösung von Entzündung. Da PC vornehmlich von der ilealen Mukosa sezerniert wird, kann man vermuten, dass dieses Phospholipid nach distal ins Kolon wandert und auf seinem Weg entlang der Kolonwand bis hin zum Rektum kontinuierlich ausgedünnt wird mit der geringsten PC-Konzentration im Rektum. Dies erklärt den Start der klinischen Manifestation der Colitis ulcerosa als Prokititis und seine Ausbreitung nach proximal bis zum Zökalpol entsprechend dem Grad der Verminderung des PC-Gehaltes im Schleim. Wenn dieses fehlende Mucus-Phosphatidylcholin bei Colitis ulcerosa mithilfe einer oralen, verzögert freigesetzten PC-Präparation wieder zugeführt wird, kann der Mangel ausgeglichen werden. In 3 randomisierten doppelblinden klinischen Studien konnte gezeigt werden, dass die Entzündung bei Colitis ulcerosa deutlich vermindert wird, ja sogar in Remission überführt wird. Diese Daten beweisen die essenzielle Rolle der Mucus-PC-Konzentration zum Schutz gegen Entzündung im Kolon. Daraus kann ein erfolgreiches neues Therapieprinzip mit oraler Applikation von verzögert im distalen Ileum freigesetztem Phosphatidylcholin entwickelt werden.

Abstract

The colonic mucus serves a first barrier towards invasion of commensal bacteria in stool. One essential component of intestinal mucus is phosphatidylcholine (PC) which represents more than 90 % of the phospholipids in mucus indicative for a selective transport of PC into this compartment. It is arranged in lamellar structures as surfactant-like particles which provide a hydrophobic surface on top of the hydrated mucus gel to prevent invasion of bacteria from the intestinal lumen. In ulcerative colitis (UC) the mucus PC content is reduced by 70 % irrespective of the state of inflammation. Thus, it could represent an intrinsic primary pathogenetic condition predisposing to bacterial invasion and precipitation of inflammation. Since PC was shown to be mainly secreted by the ileal mucosa from where it is assumed to move distally to the colon, the PC content along the colonic wall towards the rectum gradually thins out with lowest PC content in the rectum. It explains the start of the clinical manifestation of UC in the rectum and expansion from there to the upper parts of the colon. When the lacking mucus PC in the UC was supplemented by an oral, delayed released PC preparation, it was shown in three clinical trials that the inflammation improved and even resolved. The data indicate the essential role of the mucus phosphatidylcholine content for protection against inflammation in colon. This can be the basis for the development of an innovative therapy for ulcerative colitis using orally available delayed released phosphatidylcholine.

Schlüsselwörter

Phosphatidylcholin - Lecithin - Mucus - Mukosabarriere - Colitis ulcerosa

Key words

phosphatidylcholine - lecithin - mucus - mucosal barrier - ulcerative colitis
 

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