Blocking interleukin-1 in rheumatic diseases.
The role of the potent proinflammatory cytokine IL-1 in disease could clinically be investigated with the development of the IL-1 blocking agent anakinra (Kineret), a recombinant IL-1 receptor antagonist. It was first tested in patients with sepsis without much benefit but was later FDA approved for the treatment of patients with rheumatoid arthritis. More recently IL-1 blocking therapies are used successfully to treat a new group of immune-mediated inflammatory conditions, autoinflammatory diseases. These conditions include rare hereditary fever syndromes and pediatric and adult conditions of Still's disease. Recently the FDA approved two additional longer acting IL-1 blocking agents, for the treatment of cryopyrin-associated periodic syndromes (CAPS), an IL-1 dependent autoinflammatory syndrome. The study of autoinflammatory diseases revealed mechanisms of IL-1 mediated organ damage and provided concepts to a better understanding of the pathogenesis of more common diseases such as gout and Type 2 diabetes which show initial promising results with IL-1 blocking therapy.
Goldbach-Mansky
Raphaela
R
National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health, Bethesda, Maryland 20892, USA. goldbacr@mail.nih.gov
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1