title: Treating inflammation by blocking interleukin-1 in humans.
abstract: IL-1 is a master cytokine of local and systemic inflammation. With the availability of specific IL-1 targeting therapies, a broadening list of diseases has revealed the pathologic role of IL-1-mediated inflammation. Although IL-1, either IL-1α or IL-1β, was administered to patients in order to improve bone marrow function or increase host immune responses to cancer, these patients experienced unacceptable toxicity with fever, anorexia, myalgias, arthralgias, fatigue, gastrointestinal upset and sleep disturbances; frank hypotension occurred. Thus it was not unexpected that specific pharmacological blockade of IL-1 activity in inflammatory diseases would be beneficial. Monotherapy blocking IL-1 activity in a broad spectrum of inflammatory syndromes results in a rapid and sustained reduction in disease severity. In common conditions such as heart failure and gout arthritis, IL-1 blockade can be effective therapy. Three IL-1blockers have been approved: the IL-1 receptor antagonist, anakinra, blocks the IL-1 receptor and therefore reduces the activity of IL-1α and IL-1β. A soluble decoy receptor, rilonacept, and a neutralizing monoclonal anti-interleukin-1β antibody, canakinumab, are also approved. A monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α are in clinical trials. By specifically blocking IL-1, we have learned a great deal about the role of this cytokine in inflammation but equally important, reducing IL-1 activity has lifted the burden of disease for many patients.
authors.affiliation: Department of Medicine, University of Colorado Denver, Aurora, CO, United States; Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000276:immunology; D006333:Heart Failure / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053577:Interleukin-1 Receptor Accessory Protein / Q000378:metabolism; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053577:Interleukin-1 Receptor Accessory Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D011993:Recombinant Fusion Proteins; C541220:canakinumab; C531377:rilonacept
keywords: AOSD; Autoimmune; Autoinflammatory; C-reactive protein; CAPS; CRP; DIRA; FCAS; FMF; HIDS; Inflammation; NLRP12; NLRP3; NOMID; PAPA; PASH; PFAPA; SAPHO; SJIA; TNF receptor associated periodic syndrome; TRAPS; adult onset Still's disease; cryopyrin autoinflammatory periodic syndromes; deficiency of IL-1Ra; familial Mediterranean fever; familial cold autoinflammatory syndrome; hyper IgD syndrome; neonatal onset multi-inflammatory diseases; nucleotide-binding domain and leucine-rich repeat pyrin containing 12; nucleotide-binding domain and leucine-rich repeat pyrin containing 3; periodic fever, aphthous stomatitis, pharyngitis, and adenitis; pyoderma-gangrenosum, acne, and suppurativa hidradenitis; pyogenic arthritis, pyoderma gangrenosum, and acne; synovitis, acne, pustulosis, hyperostosis and osteitis; systemic-onset juvenile idiopathic arthritis