Mucosal cytokine gene expression profiles as biomarkers of response to infliximab in ulcerative colitis

Abstract

Objective. Mucosal cytokine profile determines T cell differentiation and may play an important role in the clinical course of inflammatory bowel disease (IBD). Cytokines from different T helper (Th) cell subsets are elevated in inflamed mucosa of patients with ulcerative colitis (UC), contributing to the inflammation. The aim of this study was to determine the predictive value of pre-treatment mucosal cytokine profile in response to therapy with the anti-TNF agent infliximab (IFX). Material and methods. The expression of Th1, Th17, Th2 and T-regulatory (Treg)-related cytokines was quantified by real-time PCR in mucosal biopsies from 74 UC patients before initiation of IFX induction therapy. Clinical and endoscopic effects were assessed after three infusions. Remission was defined as ulcerative colitis disease activity index (UCDAI) below 3. Results. Higher gene expression levels of IL-17A and IFN-γ were significantly associated with remission after three IFX infusions (OR = 5.4, p = 0.013 and OR = 5.5, p = 0.011, respectively). IL-17A and IFN-γ mRNA expression showed positive correlation. Th2 and Treg-related mediators were not significantly associated with clinical outcome, but were expressed at higher levels in UC patients compared with the controls. Immunohistochemistry (IHC) confirmed the presence of cells expressing both IL-17A and IFN-γ. Conclusions. High expression of Th1- and Th17-related cytokines in the mucosa of UC patients can potentially predict a favorable outcome of IFX induction therapy. Th2 and Treg-related mediators do not appear useful as predictive markers.

Key Words::

• IFN-γ
• IL-17A
• real-time quantitative PCR
• Th1
• Th17
• Th2
• Treg

Acknowledgments

We thank Marijan Remijn and Line Wilsgård for technical assistance and doctors at the Department of Gastroenterology for providing biopsies during endoscopic procedures. The project was supported by the Northern Norway Regional Health Authorities.

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