Anti-TNF-α antibodies improve intestinal barrier function in Crohn's disease.

Abstract

BACKGROUND AND AIMS:

Intestinal barrier function in Crohn's disease patients and their first degree healthy relatives is impaired. The increased intestinal permeability may result in an enhanced mucosal immune response and thereby aggravate intestinal inflammation. Humanised anti-TNF-α antibodies have been shown to be effective in the treatment of active Crohn's disease and in the treatment of entero-cutaneous fistula. The aim of the present study was to investigate the influence of anti-TNF-α antibody (infliximab) treatment on the intestinal barrier function of patients with active Crohn's disease.

METHODS:

The differential intestinal uptake of lactulose and mannitol was measured to quantify intestinal permeability in patients with long standing active Crohn's disease (n=17) directly before and seven days after treatment with infliximab (5 mg/kg bodyweight). In parallel, intestinal permeability was studied in a healthy control group (n=20). Serum samples were analysed with pulsed amperometric detection after separation on an anion exchange column.

RESULTS:

Intestinal permeability was significantly increased in all patients with Crohn's disease (L/M ratio 0.24±0.17) prior to infliximab treatment compared to the control group (L/M ratio 0.01±0.02; p-value <1×10(-7)). Treatment of patients with infliximab resulted in a marked decrease of intestinal permeability as measured by L/M ratio from 0.24±0.17 before to 0.02±0.02 (p-value <1×10(-7)) seven days after infliximab application.

CONCLUSIONS:

Treatment with anti-TNF-α antibodies improved impaired intestinal barrier function in patients with Crohn's disease. This effect may correlate to the well documented anti-inflammatory effect of TNF-α blockade in this intestinal disease.

• Authors: Rainer Noth, Eckhard Stüber, Robert Häsler, Susanna Nikolaus, Tanja Kühbacher, Jochen Hampe, Burkhard Bewig, Stefan Schreiber, Alexander Arlt
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 6 Issue 4 Pg. 464-9 (May 2012) ISSN: 1876-4479 [Electronic] England
• PMID: 22398062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Tumor Necrosis Factor-alpha
• Mannitol
• Lactulose
• Infliximab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Chromatography, High Pressure Liquid
• Crohn Disease (drug therapy, metabolism)
• Female
• Humans
• Infliximab
• Intestinal Absorption (drug effects)
• Intestinal Mucosa (metabolism)
• Intestines (drug effects)
• Lactulose (metabolism)
• Male
• Mannitol (metabolism)
• Middle Aged
• Permeability (drug effects)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, immunology)
• Young Adult