Over 20 years ago, it was first proposed that autoinflammation underpins a handful of rare monogenic disorders characterized by recurrent fever and systemic inflammation. The subsequent identification of novel, causative genes directly led to a better understanding of how the innate immune system is regulated under normal conditions, as well as its dysregulation associated with pathogenic mutations. Early on, IL-1 emerged as a central mediator for these diseases, based on data derived from patient cells, mutant mouse models and definitive clinical responses to IL-1 targeted therapy. Since that time, our understanding of the mechanisms of autoinflammation has expanded beyond IL-1 to additional innate immune processes. However, the number and complexity of IL-1-mediated autoinflammatory diseases has also multiplied to include additional monogenic syndromes with expanded genotypes and phenotypes, as well as more common polygenic disorders seen frequently by the practising clinician. In order to increase physician awareness and update rheumatologists who are likely to encounter these patients, this review discusses the general pathophysiological concepts of IL-1-mediated autoinflammation, the epidemiological and clinical features of specific diseases, diagnostic challenges and approaches, and current and future perspectives for therapy.

20 多年前，人们首次提出自身炎症是少数以反复发热和全身炎症为特征的罕见单基因疾病的基础。随后对新致病基因的鉴定直接导致了对先天免疫系统在正常条件下如何调节以及与致病性突变相关的失调的更好理解。早期，基于来自患者细胞、突变小鼠模型和对 IL-1 靶向治疗的明确临床反应的数据，IL-1 成为这些疾病的中心介质。从那时起，我们对自身炎症机制的理解已经从 IL-1 扩展到其他先天免疫过程。然而，IL-1 介导的自身炎症性疾病的数量和复杂性也成倍增加，包括具有扩展基因型和表型的其他单基因综合征，以及执业临床医生经常看到的更常见的多基因疾病。为了提高医生的认识并更新可能遇到这些患者的风湿病专家，本综述讨论了 IL-1 介导的自身炎症的一般病理生理学概念、特定疾病的流行病学和临床特征、诊断挑战和方法以及当前和未来治疗的观点。