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Global mucosal and serum cytokine profile in patients with ulcerative colitis undergoing anti-TNF therapy

Rahil Dahlén1, Maria K Magnusson, Antal Bajor

  • 1Department of Microbioloy and Immunology, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.

Scandinavian Journal of Gastroenterology
|April 17, 2015
PubMed
Abstract

Insights

Anti-tumour necrosis factor (TNF) therapy for ulcerative colitis (UC) shows distinct cytokine profiles in responders versus non-responders. Patients failing therapy exhibit a more severe pro-inflammatory cytokine profile that is less suppressed by anti-TNF treatment.

Area of Science:

  • Gastroenterology
  • Immunology
  • Molecular Biology

Background:

  • Limited understanding of anti-tumour necrosis factor (TNF) effects on cytokine profiles in ulcerative colitis (UC).
  • Identifying mechanisms can improve patient selection for anti-TNF therapy.

Purpose of the Study:

  • To determine the global mucosal and serum cytokine profiles before and during anti-TNF induction therapy in UC patients.
  • To correlate cytokine profiles with treatment response.

Main Methods:

  • Collected mucosal biopsies and serum samples from 48 UC patients before and at week 14 of anti-TNF therapy.
  • Utilized quantitative real-time PCR for mucosal cytokine mRNA expression.
  • Employed MSD MULTI-ARRAY assay for serum cytokine analysis and multivariate factor analysis for global profile evaluation.

Main Results:

  • Baseline cytokine profiles differentiated therapy responders from non-responders.
  • Responders showed lower baseline mucosal mRNA expression of IL-1β, IL-17A, IL-6, and IFN-γ.
  • Anti-TNF therapy down-regulated mucosal IL-1β and IL-6 in responders, while non-responders showed increased serum IFN-γ and IL-12p70.

Conclusions:

  • UC patients with therapy failure present a more severe pro-inflammatory cytokine profile pre-treatment.
  • This pro-inflammatory profile is less effectively suppressed by anti-TNF therapy compared to responders.
Keywords:
IBDadalimumabbiomarkercytokineinfliximabpredictiontherapy responseulcerative colitis

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