title: Anti-TNF-α antibodies improve intestinal barrier function in Crohn's disease.
abstract: OBJECTIVE
  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.affiliation: Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Noth
authors.forename: Eckhard
authors.initials: E
authors.lastname: Stüber
authors.forename: Robert
authors.initials: R
authors.lastname: Häsler
authors.forename: Susanna
authors.initials: S
authors.lastname: Nikolaus
authors.forename: Tanja
authors.initials: T
authors.lastname: Kühbacher
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bewig
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Alexander
authors.initials: A
authors.lastname: Arlt
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D000069285:Infliximab; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D007792:Lactulose / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008875:Middle Aged; D010539:Permeability / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D008353:Mannitol; D007792:Lactulose; D000069285:Infliximab