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.


OBJECTIVE
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.
Agnholt
J
J
Department of Medicine V, The MR-centre, Aarhus University Hospital, Denmark. agnholt@dadlnet.dk
Dahlerup
J F
JF
Buntzen
S
S
Tøttrup
A
A
Nielsen
S Lyhne
SL
Lundorf
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001004:Anus Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007412:Intestinal Fistula / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012002:Rectal Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D012008:Recurrence
D000911:Antibodies, Monoclonal; D016207:Cytokines; D005765:Gastrointestinal Agents; D000069285:Infliximab