Pathogenesis of IBD
Therapeutic Options to Modulate Barrier Defects in Inflammatory Bowel DiseaseHering N.A. · Schulzke J.-D.
Department of General Medicine, Charité Center 10, Campus Benjamin Franklin, Berlin, Germany
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
In inflammatory bowel disease (IBD), epithelial barrier function is impaired contributing to diarrhea by a leak flux mechanism and perpetuating inflammation by an increased luminal antigen uptake. This barrier of the intestinal epithelium is composed of the apical enterocyte membrane and the epithelial tight junction (TJ) and can be affected by TJ alterations, induction of epithelial apoptoses and appearance of gross lesions like erosions or ulcers as well as by accelerated transcytotic antigen uptake. TJ strands are reduced in Crohn’s disease (CD) and strand breaks appear. Several of the 24 claudins are concerned in CD as e.g. claudin-2, -5 and -8. The epithelial apoptotic rate has also been shown to be elevated causing focal lesions. As far as regulation is concerned, Th1 cytokines like TNF-α and interferon-γ are important for CD, while Th2 responses are dominated by interleukin (IL)-13 and TNF-α in ulcerative colitis (UC). IL-13 does stimulate epithelial apoptosis as well as upregulates claudin-2 in UC. Together with an IL-13-dependent restitution arrest, this may explain why ulcer lesions are seen already early in UC but only in advanced stages of CD. Luminal antigen uptake occurs via TJ discontinuities, epithelial gross lesions and endocytotically. Therapeutically, anti-inflammatory remedies as e.g. TNF-α antibodies are most effective in improving active IBD and in parallel repairing barrier function. Again, this is assumed to be due to reduced cytokine release in active IBD, as a result of immune cell apoptosis. However, other agents can also directly affect barrier function. Glutamine is discussed as a candidate for barrier therapy but has never been shown to have a direct barrier influence in CD, although it is an important metabolic fuel for enterocytes and has been shown to preserve barrier functions in laboratory models. Also, probiotics and TGF-β and have beneficial effects in models, but no data exist on barrier repair in IBD. In contrast, zinc has been shown to improve barrier function in CD, although the inherent mechanisms are unknown. Finally, food components can strengthen the epithelial barrier as for example the flavonoid quercetin which has been shown to upregulate claudin-4 within the epithelial TJ.
© 2009 S. Karger AG, Basel
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.