Clinical Strategies for the Blockade of IL-18 in Inflammatory Bowel Diseases
Clinical Strategies for the Blockade of IL-18 in Inflammatory Bowel Diseases
复制标题
DOI：
10.2174/13894501113149990006
复制
发表时间：
2013-11-01
影响因子：
3.2
通讯作者：
Hisamatsu, Tadakazu
中科院分区：
文献类型：
--
作者：
Kanai, Takanori;Kamada, Nobuhiko;Hisamatsu, Tadakazu
白细胞介素18（IL-18）是IL-1超家族细胞因子，参与感染、炎症和自身免疫性疾病。越来越多的证据表明IL-18在炎症和稳态中发挥双重作用。IL-18可以作为T细胞免疫的促进剂，例如1型和17型辅助T细胞应答，从而增强T细胞介导的炎症，而IL-18增加上皮细胞的屏障功能和再生，并保护宿主免受炎性刺激。尽管IL-18在炎症调节中的功能作用仍存在争议，但越来越多的证据表明IL-18在炎症性肠病（IBD）的发病机制中起作用。例如，IBD患者血清和/或粘膜IL-18和IL-18结合蛋白的水平升高。此外，在IBD患者中发现IL-18和IL-18相关分子（例如IL-18受体和/或IL-18激活剂NLRP 3）基因的多态性。因此，这些临床前数据意味着IL-18可以成为治疗IBD的新的治疗靶点。本文就IL-18在IBD动物模型和人类IBD中的生物学和生理学作用进行综述，为IL-18阻断策略的发展提供一个框架。
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.