Clinical Strategies for the Blockade of IL-18 in Inflammatory Bowel Diseases

Author(s): Takanori Kanai, Nobuhiko Kamada, Tadakazu Hisamatsu.

Journal Name: Current Drug Targets

Volume 14 , Issue 12 , 2013

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Abstract:

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.

Keywords: IL-18, IL-18BP, inflammatory bowel disease, Crohn’s disease, ulcerative colitis.

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Article Details

VOLUME: 14
ISSUE: 12
Year: 2013
Page: [1392 - 1399]
Pages: 8
DOI: 10.2174/13894501113149990006
Price: $58

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