title: Clinical strategies for the blockade of IL-18 in inflammatory bowel diseases.
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.
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. takagast@sc.itc.keio.ac.jp.
authors: Takanori
authors: T
authors: Kanai
authors: Nobuhiko
authors: N
authors: Kamada
authors: Tadakazu
authors: T
authors: Hisamatsu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000473:pathology*; D020382:Interleukin-18 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D058990:Molecular Targeted Therapy; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011110:Polymorphism, Genetic; D053700:Receptors, Interleukin-8 / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D053700:Receptors, Interleukin-8