The influence of cytokines on the complex pathology of ulcerative colitis

Autoimmun Rev. 2022 Mar;21(3):103017. doi: 10.1016/j.autrev.2021.103017. Epub 2021 Dec 10.

Abstract

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-α, α4β7 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-1β, IL-6, tumor necrosis factor-α, 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.

Keywords: Complex pathology; Cytokine; Ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / pathology
  • Cytokines
  • Humans
  • Intestinal Mucosa
  • Tumor Necrosis Factor-alpha / therapeutic use

Substances

  • Cytokines
  • Tumor Necrosis Factor-alpha