Journal
EUROPEAN JOURNAL OF INTERNAL MEDICINE
Volume 21, Issue 3, Pages 157-163Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejim.2010.03.005
Keywords
IL-1 beta; Anakinra; Canakinumab; Rilonacept; Autoinflammatory syndromes
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NLRP3 inflammasome activation and IL-1 beta secretion have recently emerged as a central mechanism in the pathogenesis of disease. Genetically defined syndromes like cryopyrin-associated periodic syndromes (CAPS, cryopyrinopathies) and familial Mediterranean fever (FMF) or diseases associated with NLRP3 activation by danger signals like gout, pseudogout, Alzheimer's disease or type 2 diabetes are included in this group of diseases. The contribution of anakinra, a recombinant, nonglycosylated human IL-1 receptor antagonist, in both the identification and treatment of such syndromes was considerable. Recently, rilonacept, a long-acting IL-1 receptor fusion protein, and canakinumab, a fully humanized anti-IL-1 beta monoclonal antibody, have been developed, with the intention to further extent IL-1 beta inhibition treatment strategies to a broader spectrum of disorders beyond the characterized autoinflammatory syndromes, offering a more favorable administration profile. On the other hand, the developed caspase-1 inhibitors, even though effective in experimental models, were not proven efficient in the treatment of inflammatory diseases. (C) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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