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-α, interferon-γ 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-α 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-γ production in in vitro cell cultures. Fistula healing was associated with reduced production of interferon-γ, tumour necrosis factor-α 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-α and interferon-γ production are different in responders and at relapse.