Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease.
OBJECTIVE
A primary defect of the tight junctions and, hence, increased intestinal epithelial permeability has been proposed as a basic pathogenic event in Crohn's disease. Challenge of the mucosal immune system by the commensal gut flora would then result in chronic inflammation. Alternatively, increased permeability could be the result of inflammation. Our aim was to study intestinal permeability in refractory Crohn's disease before and after treatment with monoclonal chimeric antibodies directed against tumor necrosis factor (TNF) to investigate whether the abnormal permeability persists after control of inflammation.


METHODS
Twenty-three patients with active Crohn's disease were evaluated before and 4 wk after a single infusion of 5 mg/kg infliximab. Intestinal permeability was studied by measurement of urinary excretion of 51Cr-EDTA after oral intake.


RESULTS
The increased permeation of 51Cr-EDTA through the small intestine (1.63% interquartile range [IQR] 1.06-2.07) and the overall permeation (3.27% IQR 2.40-4.38) before therapy decreased significantly after infliximab infusion to values (1.04% IQR 0.74-1.54 and 2.42% IQR 2.03-2.80, respectively) in the range of those found in normal volunteers (1.12% IQR 0.85-1.58 and 2.28% IQR 1.88-2.86, respectively).


CONCLUSIONS
Inhibiting the proinflammatory cytokine tumor necrosis factor dramatically reduces gut inflammation and largely restores the gut barrier in Crohn's disease. Our data confirm the central role of TNF in gut barrier modulation in inflammatory conditions in vivo.
Department of Gastroenterology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium.
Peter
P
Suenaert
Veerle
V
Bulteel
Liesbeth
L
Lemmens
Maja
M
Noman
Benny
B
Geypens
Gert
G
Van Assche
Karel
K
Geboes
Jan L
JL
Ceuppens
Paul
P
Rutgeerts
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002860:Chromium Radioisotopes; D003424:Crohn Disease / Q000188:drug therapy* / Q000503:physiopathology*; D004492:Edetic Acid / Q000493:pharmacokinetics / Q000652:urine; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007413:Intestinal Mucosa / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D002860:Chromium Radioisotopes; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D004492:Edetic Acid; D000069285:Infliximab