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

Aliment Pharmacol Ther. 2003 Mar 1;17(5):703-10. doi: 10.1046/j.1365-2036.2003.01487.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • Gastrointestinal Agents
  • Infliximab