Mucosal Cytokine Expression Associated With Deep Endoscopic Mucosal Healing in Ulcerative Colitis

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of unknown cause, for which no curative treatments have been developed. Cytokines play an important role in the pathogenesis of UC, and therapies targeting specific cytokines have been successful in treating refractory UC. The purpose of this study was to measure mucosal cytokines in UC and identify those that contribute to nonrelapsing mucosal healing (MH) diagnosed by endoscopy. Methods: This prospective, observational study included 163 patients with UC. The mucosa was evaluated by the Mayo Endoscopic Subscore (MES) and linked color imaging (LCI) at the time of endoscopy, and cytokine mRNA expression in biopsy tissue taken from the same site was quantified by real-time PCR and compared with endoscopic findings. The relationship between cytokine mRNA expression and endoscopic findings was investigated. Results: Cytokines such as IFN gamma, IL-1 beta, IL-8, IL-17A, and IL-23 were significantly elevated in proportion to endoscopic severity of MES and LCI classification. Interestingly, we found differences in the expression of cytokines (eg, IL-22 and IL-33) between MES and LCI classification according to disease severity. Additionally, pathway analysis based on RNA sequencing comparing LCI-A and LCI-B in patients diagnosed as MES 0 revealed that IL-5 and IL-6 are involved in the finer differences in endoscopic mucosal redness. Conclusions: This study is the first to report the correlation between mucosal cytokine expression and the pathogenesis of MH in UC and supports the contribution of specific cytokines as molecular markers of MH or in the pathogenesis of MH in UC.