期刊
CURRENT DRUG TARGETS
卷 14, 期 12, 页码 1392-1399出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/13894501113149990006
关键词
IL-18; IL-18BP; inflammatory bowel disease; Crohn's disease; ulcerative colitis
资金
- Japanese Ministry of Education, Culture, Sports, Science and Technology
- Japanese Ministry of Health, Labour and Welfare
Interleukin 18 (IL-18) is an IL-1 super family cytokine that is involved in infection, inflammation and autoimmune diseases. Mounting evidence suggests that IL-18 exert a dual role in inflammation and homeostasis. IL-18 can act as a promoter of T cell immunities, such as type 1 and 17 helper T cell responses, and thus enhances T cell-mediated inflammation, whereas IL-18 increases the barrier function and regeneration of epithelial cells and protects the host from inflammatory stimuli. Although the functional role of IL-18 in regulation of inflammation remains controversial, accumulating evidence indicates the contribution of IL-18 to the pathogenesis of inflammatory bowel diseases (IBD). For example, levels of serum and/or mucosal IL-18 and IL-18 binding protein are elevated in the patients with IBD. Furthermore, polymorphisms in IL-18 and IL-18-related molecules, such as the IL-18 receptor and/or an IL-18 activator NLRP3, genes are found in the patients with IBD. Thus, these preclinical data imply that IL-18 can be a novel therapeutic target for the treatment of IBD. In this review, we focus on IL-18 biology and physiological roles in animal models and human IBD, to provide an outline for development of IL-18 blockade strategies.
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