Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Front Immunol. 2022 Jul 25;13:930141. doi: 10.3389/fimmu.2022.930141. eCollection 2022.
: Interleukin-18 (IL-18) is a proinflammatory cytokine that promotes various innate immune processes related to infection, inflammation, and autoimmunity. Patients with systemic juvenile idiopathic arthritis and adult-onset Still's disease exhibit chronic excess of serum IL-18, which is associated with a high incidence of macrophage activation syndrome (MAS), although the mechanisms of IL-18 regulation in such diseases remain largely unknown. Similar elevation of serum IL-18 and susceptibility to MAS/hemophagocytic lymphohistiocytosis (HLH) have been reported in monogenic diseases such as X-linked inhibitor of apoptosis deficiency (i.e., X-linked lymphoproliferative syndrome type 2) and NLRC4-associated autoinflammatory disease. Recent advances in molecular and cellular biology allow the identification of other genetic defects such as defects in , , and that result in high serum IL-18 levels and hyperinflammation. Among these diseases, chronic excess of serum IL-18 appears to be linked with severe hyperinflammation and/or predisposition to MAS/HLH. In this review, we focus on recent findings in inflammatory diseases associated with and probably attributable to chronic excess of serum IL-18 and describe the clinical and therapeutical relevance of understanding the pathology of this group of diseases.
白细胞介素-18（IL-18）是一种促炎细胞因子，可促进与感染、炎症和自身免疫有关的各种固有免疫过程。全身性幼年特发性关节炎和成人Still 病患者表现出慢性血清 IL-18 过量，这与巨噬细胞活化综合征（MAS）的高发生率相关，尽管此类疾病中 IL-18 调节的机制在很大程度上仍不清楚。在单基因疾病中，如 X 连锁凋亡抑制因子缺陷（即 X 连锁淋巴组织增生性疾病 2 型）和 NLRC4 相关自身炎症性疾病中，也有血清 IL-18 升高和 MAS/噬血细胞性淋巴组织细胞增生症（HLH）易感性的类似报道。分子和细胞生物学的最新进展使得能够鉴定其他遗传缺陷，如 、 和 ，导致血清 IL-18 水平升高和炎症过度。在这些疾病中，血清 IL-18 的慢性过量似乎与严重的炎症过度和/或 MAS/HLH 的易感性有关。在这篇综述中，我们重点介绍了与慢性血清 IL-18 过量相关且可能归因于慢性血清 IL-18 过量的炎症性疾病的最新发现，并描述了理解这群疾病病理学的临床和治疗相关性。
