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

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.