Remicade intestinal permiability

[my little penguin]

OBJECTIVES: 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).
CONCLUSION: 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.

The American Journal of Gastroenterology (2002) 97, 2000–2004; doi:10.1111/j.1572-0241.2002.05914.x

Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease

Peter Suenaert MD1, Veerle Bulteel MSc1, Liesbeth Lemmens MSc1, Maja Noman MD1, Benny Geypens PhDMSc1, Gert Van Assche MD, PhD1, Karel Geboes MD, PhD2, Jan L Ceuppens MD, PhD3 and Paul Rutgeerts MD, PhD1

1Department of Gastroenterology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium
2Department of Pathology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium
3Laboratory of Experimental Immunology, University Hospital Gasthuisberg, Catholic University Leuven, Leuven, Belgium
Correspondence: P Rutgeerts, MD, PhD, FRCP, Department of Gastroenterology, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.

Received 10 July 2001; Accepted 3 January 2002.





From
http://www.nature.com/ajg/journal/v97/n8/abs/ajg2002518a.html