The influence of cytokines on the complex pathology of ulcerative colitis

Ulcerative colitis (UC) specifically affects the colon and rectum through multifactorial mechanisms associated with genetic alterations, environmental factors, microbiota, and mucosal immune dysregulation. In patients with corticosteroid-refractory UC, current therapies primarily employ antibodies against tumor necrosis factor-alpha, alpha 4 beta 7 integrin, and interleukin (IL)-12/23 p40; and a small-molecule Janus kinase inhibitor. Despite these revolutionary molecular targeting therapies introduced during the last two decades, 30%-55% of patients fail to respond such molecular targeting agents in the induction phase, requiring changes in treatment. Here we review basic and clinical research aimed to address this problem, focusing on the pathogenic effects of cytokines produced by innate and adaptive immune cells. For example, IL-1 beta, IL-6, tumor necrosis factor-alpha, T helper (Th) 1-, Th2-, and Th17-associated cytokines are expressed at relatively higher levels in the intestinal tissues of patients with UC. However, their expression levels depend on disease stage and patient characteristics. The complex pathology of UC may induce differences in responses to therapy. The findings of such studies strongly support the argument that future targeted therapies must focus on differences in cytokine levels associated with the stages of UC as well as on the distinct cytokine expression profiles of individual patients.

Automated summary

Ulcerative colitis (UC) is specifically affected by genetic alterations, environmental factors, microbiota, and mucosal immune dysregulation, leading to a lack of response in 30%-55% of patients to current therapies. The expression levels of cytokines associated with treatment depend on disease stage and patient characteristics, suggesting that future targeted therapies should focus on these differences and individual cytokine profiles.