Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University, Milan, Italy.
Dipartimento of Clinical Sciences (Internal Medicine, Anesthesia and Resuscitation, and Cardiology), Rheumatology Unit, Sapienza University of Rome, Rome, Italy.
Autoimmun Rev. 2021 Mar;20(3):102763. doi: 10.1016/j.autrev.2021.102763. Epub 2021 Jan 20.
The interleukin (IL)-1 family member IL-1α is a ubiquitous and pivotal pro-inflammatory cytokine. The IL-1α precursor is constitutively present in nearly all cell types in health, but is released upon necrotic cell death as a bioactive mediator. IL-1α is also expressed by infiltrating myeloid cells within injured tissues. The cytokine binds the IL-1 receptor 1 (IL-1R1), as does IL-1β, and induces the same pro-inflammatory effects. Being a bioactive precursor released upon tissue damage and necrotic cell death, IL-1α is central to the pathogenesis of numerous conditions characterized by organ or tissue inflammation. These include conditions affecting the lung and respiratory tract, dermatoses and inflammatory skin disorders, systemic sclerosis, myocarditis, pericarditis, myocardial infarction, coronary artery disease, inflammatory thrombosis, as well as complex multifactorial conditions such as COVID-19, vasculitis and Kawasaki disease, Behcet's syndrome, Sjogren Syndrome, and cancer. This review illustrates the clinical relevance of IL-1α to the pathogenesis of inflammatory diseases, as well as the rationale for the targeted inhibition of this cytokine for treatment of these conditions. Three biologics are available to reduce the activities of IL-1α; the monoclonal antibody bermekimab, the IL-1 soluble receptor rilonacept, and the IL-1 receptor antagonist anakinra. These advances in mechanistic understanding and therapeutic management make it incumbent on physicians to be aware of IL-1α and of the opportunity for therapeutic inhibition of this cytokine in a broad spectrum of diseases.
白细胞介素 (IL)-1 家族成员 IL-1α 是一种普遍存在且至关重要的促炎细胞因子。IL-1α 前体在健康状态下几乎存在于所有细胞类型中，但在坏死细胞死亡时作为生物活性介质释放。IL-1α 也由受损组织内浸润的髓样细胞表达。该细胞因子与 IL-1 受体 1 (IL-1R1) 结合，IL-1β 也是如此，并诱导相同的促炎作用。作为一种在组织损伤和坏死细胞死亡时释放的生物活性前体，IL-1α 是许多以器官或组织炎症为特征的疾病发病机制的核心。这些疾病包括影响肺和呼吸道的疾病、皮肤病和炎症性皮肤疾病、系统性硬化症、心肌炎、心包炎、心肌梗塞、冠心病、炎症性血栓形成，以及 COVID-19、血管炎和川崎病、贝赫切特综合征、干燥综合征和癌症等复杂的多因素疾病。这篇综述说明了 IL-1α 与炎症性疾病发病机制的临床相关性，以及靶向抑制这种细胞因子治疗这些疾病的原理。有三种生物制剂可降低 IL-1α 的活性；单克隆抗体 bermekimab、IL-1 可溶性受体 rilonacept 和 IL-1 受体拮抗剂 anakinra。这些在机制理解和治疗管理方面的进展使得医生有必要了解 IL-1α 及其在广泛疾病中抑制这种细胞因子的机会。
