Mucosal gene expression of inflammatory cytokines as biomarkers for predicting treatment response in patients with inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic disorder that involves a complex cytokine network. Despite an array of treatment options, no predictive biomarkers for response to IBD treatment have been established. We aimed to identify predictive biomarkers of therapeutic effectiveness in patients with IBD. Inflammatory cytokine gene expression was analyzed in biopsied samples of the inflamed ileal or colonic mucosa from patients with ulcerative colitis (UC) and Crohn's disease (CD). The relationship between mucosal cytokine gene expression and therapeutic response to corticosteroids and anti-TNF-α antibodies was investigated. Cytokines representative of helper T cell 2 (interleukin (IL)-4 and 5) and helper T cell 17 (IL-17, CCL20, IL-21, and IL-22) were higher in UC than CD. CCL11, CXCL1, CXCL2, CXCL8, OSM, and TGF-β expression was elevated in both UC and CD patients in corticosteroid-dependent cases compared to corticosteroid-free remission cases, with CXCL8 representing the best biomarker. IL-1α, IL-1β, IL-1RN, OSM, and IL-6 expression was elevated in anti-TNF-α antibody-resistant cases. RELA and STAT3 expression was increased in corticosteroid-dependent and anti-TNF-α antibody nonresponder patients, respectively. Mucosal chemokine, IL-1, and IL-6 gene expression can predict corticosteroid-dependent and anti-TNF-α antibody refractory cases. IL-1 and IL-6 and associated pathways are potential therapeutic targets for these cases. Clinical trial registration The study formed part of a comprehensive clinical trial listed under the University Medical Information Network—Clinical Trial Registration (UMIN-CTR) number 000041268, as initiated on August 1, 2020.