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

Abstract

Background and objective. The knowledge of the effects of anti-tumour necrosis factor (TNF) treatment on the global cytokine profile in patients with ulcerative colitis (UC) is limited. A better understanding of these mechanisms could improve the ability to select patients that should undergo the therapy. Therefore, the aim was to determine the global mucosal and serum cytokine profile before and during induction therapy with anti-TNF in UC patients. Materials and methods. In total, mucosal biopsies (n = 28) and serum samples (n = 42) were collected from UC patients (total n = 48) before anti-TNF therapy. At week 14 response to the therapy was evaluated and again mucosal biopsies (n = 14) and serum samples (n = 42) were collected. Quantitative real-time PCR was used to determine mucosal cytokine mRNA expression and the MSD MULTI-ARRAY assay system platform was used for analysis of cytokines in serum. The global cytokine profile was evaluated by multivariate factor analysis. Results. At baseline, the global profile of mucosal cytokine mRNA expression and serum cytokines discriminated therapy responders from non-responders. Responders had lower mucosal mRNA expression of interleukin 1β (IL-1β), IL-17A, IL-6 and interferon γ (IFN-γ) than non-responders. Fourteen weeks after therapy start mucosal IL-1β and IL-6 were down-regulated in therapy responders but not in non-responders. At week 14, serum levels of IL-6 were decreased in therapy responders whereas IFN-γ and IL-12p70 were increased in non-responders. Conclusions. Our data suggest that patients with a therapy failure have a more severe pro-inflammatory cytokine profile before start of anti-TNF treatment, which is less well suppressed by the treatment as compared to therapy responders.

Key Words:

• adalimumab
• biomarker
• cytokine
• IBD
• infliximab
• prediction
• therapy response
• ulcerative colitis

Acknowledgements

We would like to thank the Genomics Core Facility at the Sahlgrenska Academy, University of Gothenburg for providing expertise during RT-PCR analysis. This study was supported by the Swedish Medical Research Council (VR-M), the Health & Medical Care Committee of the Regional Executive Board Region in Västra Götaland, Mag-Tarmfonden, the Sahlgrenska University Hospital (LUA-ALF), the Swedish Society of Medicine and the foundations of Ruth and Richard Julin, Claes Groshinsky, Wilhelm and Martina Lundgren and Adlerbertska. The study sponsors had no involvement in the study design, sample collection, data analysis, data interpretation or writing of the manuscript. R Dahlén, L Öhman, MK Magnusson, and H Strid contributed to the conception and design of the study. R Dahlén performed the experiments. H Strid, A Bajor, A Lasson and KA Ung recruited and enrolled patients in the study. All the authors contributed to the analysis and interpretation of data. R Dahlén, MK Magnusson and L Öhman wrote the manuscript and H Strid, A Bajor, A Lasson and KA Ung critically reviewed and approved the final draft.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.