Sanders Nathan L, Mishra Anil
Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorders Center, Tulane University School of Medicine, New Orleans, LA 70112, United States of America; Tulane University in Neuroscience and Biological Chemistry, Tulane University, New Orleans, LA, United States of America.
Department of Medicine, Section of Pulmonary Diseases, Tulane Eosinophilic Disorders Center, Tulane University School of Medicine, New Orleans, LA 70112, United States of America.
Cytokine Growth Factor Rev. 2016 Dec;32:31-39. doi: 10.1016/j.cytogfr.2016.07.001. Epub 2016 Jul 15.
Interleukin (IL)-18 is an IL-1 family cytokine expressed by macrophages, dendritic cells, epithelial cells, and keratinocytes and is implicated in various aspects of both the innate and adaptive immune systems. IL-18 signals similar to IL-1β intracellularly to activate gene transcription. Since its discovery, IL-18 has been demonstrated to play a key role in pathogen defense from helminths and some bacteria. Recently however, evidence has accumulated that IL-18 expression is increased in many presentations of allergic disease. A pathologic role for IL-18 includes stimulating mast cell and basophil degranulation, recruiting granulocytes to sites of inflammation, increasing cytotoxic activity of natural killer (NK) and NK-T cells, inducing Immunoglobulin (Ig)E production and isotype switching, and affecting a broad range of T cells to promote a type II helper T cell (Th2) response. Evidence and importance of these effects are presented, including novel results from our lab implicating IL-18 in the direct expansion of mast cells, basophils, and other myeloid-lineage cells from bone-marrow precursors. The development of urticaria, asthma, dermatitis, rhinitis, and eosinophilic disorders all have demonstrated correlations to increased IL-18 levels either in the tissue or systemically. IL-18 represents a novel site of immune regulation in not only allergic conditions, but also autoimmune diseases and other instances of aberrant immune functioning. Diagrammatic summarized abstract for readers convinance is presented in Fig. 1.
白细胞介素（IL）-18是一种由巨噬细胞、树突状细胞、上皮细胞和角质形成细胞表达的IL-1家族细胞因子，参与固有免疫系统和适应性免疫系统的多个方面。IL-18在细胞内的信号传导类似于IL-1β，可激活基因转录。自发现以来，IL-18已被证明在抵御蠕虫和某些细菌的病原体防御中起关键作用。然而，最近有证据表明，在许多过敏性疾病表现中IL-18表达增加。IL-18的病理作用包括刺激肥大细胞和嗜碱性粒细胞脱颗粒、将粒细胞募集到炎症部位、增加自然杀伤（NK）细胞和NK-T细胞的细胞毒性活性、诱导免疫球蛋白（Ig）E产生和同种型转换，以及影响多种T细胞以促进II型辅助性T细胞（Th2）反应。本文介绍了这些作用的证据及其重要性，包括我们实验室的新结果，表明IL-18参与骨髓前体来源的肥大细胞、嗜碱性粒细胞和其他髓系细胞的直接扩增。荨麻疹、哮喘、皮炎、鼻炎和嗜酸性疾病的发生均已证明与组织或全身IL-18水平升高有关。IL-18不仅在过敏性疾病中，而且在自身免疫性疾病和其他免疫功能异常的情况下，均代表了一个新的免疫调节位点。为方便读者，图1给出了示意性总结摘要。
