Blocking Interleukin-1 in Rheumatic Diseases

Its Initial Disappointments and Recent Successes in the Treatment of Autoinflammatory Diseases


  • Raphaela Goldbach-Mansky

    1. National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health, Bethesda, Maryland, USA
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Address for correspondence: Raphaela Goldbach-Mansky, M.D., M.H.S., NIH/NIAMS, Building 10, Rm. 6D-47B, 10 Center Dr., Bethesda, MD 20892.


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.