2. Academic Validation
  3. Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases

Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases

  • Autoimmun Rev. 2021 Mar;20(3):102763. doi: 10.1016/j.autrev.2021.102763.
Giulio Cavalli 1,  Serena Colafrancesco 2,  Giacomo Emmi 3,  Massimo Imazio 4,  Giuseppe Lopalco 5,  Maria Cristina Maggio 6,  Jurgen Sota 7,  Charles A Dinarello 8
Affiliations

Affiliations

  • 1 Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS San Raffaele Scientific Institute; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: cavalli.giulio@hsr.it.
  • 2 Dipartimento of Clinical Sciences (Internal Medicine, Anesthesia and Resuscitation, and Cardiology), Rheumatology Unit, Sapienza University of Rome, Rome, Italy.
  • 3 Department of Experimental and Clinical Medicine, Careggi University Hospital, Firenze, Italy.
  • 4 University Division of Cardiology, Cardiovascular and Throracic Department, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
  • 5 Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Bari, Italy.
  • 6 Department of Health Promotion, Maternal and Infantile Care, Department of Internal Medicine and Medical Specialties "G. D'Alessandro", University of Palermo, Palermo, Italy.
  • 7 Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
  • 8 Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: cdinare333@aol.com.
PMID: 33482337 DOI: 10.1016/j.autrev.2021.102763
Abstract

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.

Keywords

Autoimmunity; Cancer; Cytokines; IL-1; IL-1α; IL-1β; Inflammation.

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