| 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)
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| Journal | Alimentary pharmacology & therapeutics
(Aliment Pharmacol Ther)
Vol. 17
Issue 5
Pg. 703-10
(Mar 1 2003)
ISSN: 0269-2813 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
|
