title: Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies.
abstract: The inflammatory cytokines IL-1α and IL-1β orchestrate local and systemic inflammatory responses underlying a broad spectrum of diseases. Three agents for reducing IL-1 activities are currently available. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist. Anakinra binds to the IL-1 receptor and prevents the activity of IL-1α and IL-1β. The soluble decoy receptor rilonacept and the neutralizing mAb canakinumab block IL-1β. A mAb directed against the IL-1 receptor and a neutralizing anti-human IL-1α are in clinical trials. The availability of therapies specifically targeting IL-1 unveiled the pathological role of IL-1-mediated inflammation in a broadening list of diseases. Conditions effectively treated with agents blocking IL-1 range from classic rheumatic diseases, such as RA and gout, to autoinflammatory syndromes, such as systemic JIA and FMF. However, IL-1 antagonism is also effective against highly prevalent inflammatory diseases, namely cardiovascular diseases and type 2 diabetes, conditions that are frequently encountered as co-morbidities in patients with rheumatic diseases. Thereby, IL-1 inhibition has the potential to lift the burden of disease for patients with rheumatic conditions, but also to provide clinical benefits beyond the efficacy on osteoarticular manifestations.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO, USA, Division of Internal Medicine and Clinical Immunology, IRCCS San Raffaele Scientific Institute, Milan, Italy and cavalli.giulio@gmail.com.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cavalli
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO, USA, Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D015897:Comorbidity; D056660:Hereditary Autoinflammatory Diseases / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; C541220:canakinumab; C531377:rilonacept
keywords: IL-1α; IL-1β; anakinra; autoinflammatory syndromes; canakinumab; cardiovascular disease; diabetes; interleukin-1; rheumatoid arthritis