title: Effects of anti-tumour necrosis factor, interleukin-10 and antibiotic therapy in the indometacin-induced bowel inflammation rat model.
abstract: BACKGROUND
  The administration of indometacin to rats increases intestinal permeability and induces inflammatory pathology of the small bowel. This represents a potential model for Crohn's disease.
  
  
  OBJECTIVE
  To analyse the pathogenic role of T cells, tumour necrosis factor and bacterial flora in indometacin-induced changes in small bowel permeability and inflammation.
  
  
  METHODS
  Rats were given indometacin, 13 mg/kg, on day 1 and day 2. The effects of antibiotic (metronidazole, aztreonam and amoxicillin/clavulanic acid), anti- tumour necrosis factor and interleukin-10 therapy were evaluated. The parameters used were weight change, serum haemoglobin, chromium-51 ethylenediaminetetra-acetate permeability and macro-and microscopic score on day 5. Results in conventionally harboured rats were compared with those in T-cell-free rats. Additional in vitro experiments were carried out to test the effect of metronidazole on tumour necrosis factor production.
  
  
  RESULTS
  Indometacin administration resulted in small bowel ulcers and inflammation, independently of T cells. Metronidazole was more potent than amoxicillin/clavulanic acid and anti-tumour necrosis factor in improving the indometacin-induced small bowel inflammation. Only part of the efficacy was through improvement of increased intestinal permeability. Aztreonam and interleukin-10 had no effect. Metronidazole also suppressed in vitro lipopolysaccharide-induced tumour necrosis factor production, suggesting a therapeutic effect of this drug through the inhibition of tumour necrosis factor.
  
  
  CONCLUSIONS
  These data implicate anaerobic bacteria and tumour necrosis factor production, but not T cells, as essential elements of the pathogenesis of indometacin-induced small bowel inflammation. Tumour necrosis factor is also involved in the change in intestinal permeability. Metronidazole was the most efficacious drug in this model, probably because it suppressed anaerobic bacteria and directly inhibited tumour necrosis factor production.
authors.affiliation: Laboratory of Experimental Immunology, University Hospital and Catholic University of Leuven, Belgium. Stefaan.Colpaert@med.kuleuven.ac.be
authors.forename: S
authors.initials: S
authors.lastname: Colpaert
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: De Greef
authors.forename: P
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: J L
authors.initials: JL
authors.lastname: Ceuppens
authors.forename: K
authors.initials: K
authors.lastname: Geboes
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D001398:Aztreonam / Q000494:pharmacology*; D001421:Bacteria, Anaerobic; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects; D007249:Inflammation / Q000503:physiopathology*; D016753:Interleukin-10 / Q000494:pharmacology*; D008795:Metronidazole / Q000494:pharmacology*; D008997:Monobactams / Q000494:pharmacology*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008997:Monobactams; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008795:Metronidazole; D019980:Amoxicillin-Potassium Clavulanate Combination; D001398:Aztreonam; D007213:Indomethacin