摘要：

Interleukin 1 (IL-1) is a crucial mediator of the inflammatory response, playing an important part in the body's natural responses and the development of acute pathological conditions leading to chronic inflammation and tissue destruction. In the last decades, specific IL-1-targeting therapies have produced beneficial effects in a wide spectrum of IL-1 driven diseases, the most dramatic one being autoinflammatory disorders. Indeed, IL-1 continues to be a key attractive therapeutic target for many inflammatory, metabolic, skin, and heart disease. The main purpose of this Research Topic is to discuss and evaluate some current knowledge on IL-1 biology and the rational approach toward its blockade in different conditions. The topic covers both basic scientific as well as clinical aspects and includes 8 reviews, 8 original articles, 1 perspective, and 1 opinion. The topic focusing mainly on IL-1? and its antagonism does not preclude for the importance of other members of the IL-1 family. Back to history, Dayer et al. reminds the discovery of the monocytic origin of IL-1 in Rheumatology, the seminal description of the mechanism of IL-1 receptor antagonist (IL-1Ra) acting as ligand binding to its IL-1 receptor and its change levels in serum of adult-onset Still's disease. The inflammasome, the expansion of the IL-1 family, as well as the role on the IL-1 and IL-1Ra in crystal induced arthropathies, osteoarthritis and in cartilage and bone biology, are discussed. Following a useful update on IL-1, Cavalli and Dinarello review the importance of IL-1 blockade by anakinra, the recombinant form of the naturally occurring IL-1Ra. The Authors focus on anakinra treatment of a broad spectrum of acute as well as chronic inflammatory diseases, ranging from rare autoinflammatory diseases to common conditions such as gout and rheumatoid arthritis, type 2 diabetes, atherosclerosis, and acute myocardial infarction. The efficacy of IL-1 blockade in autoinflammatory-associated skin diseases is extensively described in the article by Fenini et al. The Authors review the different IL-1? antagonists available in the market, inflammasome inhibitors and IL-1α and IL-18 blockers under development and investigation in both monogenic and polygenic autoinflammatory diseases (Note of Editors: The biotherapies in adult-onset Still's disease and other rare inflammatory disorders, including blockade of IL-18 has been more recently discussed in the editorial of Guilpain et al., 2018 ). The use of IL-1 inhibitors in the management of systemic juvenile idiopathic arthritis is discussed in the article of Giancane et al. As not all patients respond to anti-IL-1 therapy in that disease, the Authors argue about the possible causes of the different clinical responses focusing on the heterogeneous nature of systemic juvenile idiopathic arthritis. Dusser and Koné-Paut discuss the key role of IL-1 inhibition in Kawasaki disease which shares phenotypical and immunological similarities with systemic juvenile idiopathic arthritis. Few clinical trials on IL-1 blockade in young patients affected with Kawasaki disease have been conducted and the Authors discuss the importance of this therapeutic approach to treat refractory forms. The article of Colafrancesco et al. reports clinical results obtained from a large Italian multicentric retrospective observational study conducted in patients with adult-onset Still's disease. In this study, the efficacy and safety of two IL-1 inhibitors are evaluated in patient's refractory to other therapies. A good response was noted at 3 months after therapy onset in both groups. Peiró et al. summarize the main experimental and clinical findings obtained with pharmacological IL-1β inhibitors in patients with diabetes mellitus and cardiovascular complications and discuss the perspectives of IL-1β inhibitors as novel therapeutic tools for treating these patients. (Note of Editors: In fact, just recently a large clinical study "CANTOS" shows promising results both in biological parameters and clinical outcomes (Ridker et al., 2017 ). At the 201

展开