Response, relapse and mucosal immune regulation after infliximab treatment in fistulating Crohn's disease.

• Abstract: BACKGROUND: Infliximab reduces mucosal inflammation in some, but not all, patients with Crohn's disease. AIM: To monitor clinical data and changes in mucosal cytokine levels after infliximab treatment to identify differences between responders and non-responders. METHODS: Twenty-six patients with fistulating Crohn's disease received three infliximab infusions at weeks 0, 2 and 6. Follow-up was for 1 year and included clinical examination, colonoscopy, ano-rectal ultrasound and magnetic resonance imaging. Biopsies were taken at weeks 0, 8, 26 and 52. Cell cultures were established and analysed for tumour necrosis factor-alpha, interferon-gamma and interleukin-10 levels, and related to clinical status and fistula healing. RESULTS: Eleven of 15 patients (73%) with active disease (Crohn's disease activity index > 150) obtained remission (Crohn's disease activity index < 150) at 8 weeks. In in vitro cell cultures, there was reduced tumour necrosis factor-alpha and interleukin-10 production at week 26, with the latter persistent throughout the study period. When the disease deteriorated or relapsed, there was increased interferon-gamma production in in vitro cell cultures. Fistula healing was associated with reduced production of interferon-gamma, tumour necrosis factor-alpha and interleukin-10. CONCLUSIONS: Infliximab down-regulates mucosal immune activation in Crohn's disease. Monitoring of mucosal cytokine levels after infliximab treatment by whole biopsy cultures may be useful as interleukin-10, tumour necrosis factor-alpha and interferon-gamma production are different in responders and at relapse.
• Authors: J Agnholt, J F Dahlerup, S Buntzen, A Tøttrup, S Lyhne Nielsen, E Lundorf (Affiliation: Department of Medicine V, The MR-centre, Aarhus University Hospital, Denmark. agnholt at dadlnet.dk)
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 17 Issue 5 Pg. 703-10 (Mar 1 2003) ISSN: 0269-2813 [Print] England
• PMID: 12641520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Cytokines
• Gastrointestinal Agents
• infliximab

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• Anus Diseases (complications, metabolism, pathology)
• Cells, Cultured
• Crohn Disease (drug therapy, metabolism, pathology)
• Cytokines (metabolism)
• Female
• Gastrointestinal Agents (therapeutic use)
• Humans
• Intestinal Fistula (complications, metabolism, pathology)
• Intestinal Mucosa (immunology)
• Male
• Middle Aged
• Rectal Diseases (complications, metabolism, pathology)
• Recurrence