Targeting IL-1β in disease; the expanding role of NLRP3 inflammasome

被引:117
作者
Mitroulis, Ioannis [1 ]
Skendros, Panagiotis [1 ]
Ritis, Konstantinos [1 ]
机构
[1] Democritus Univ Thrace, Dept Internal Med 1, Alexandroupolis, Greece
关键词
IL-1; beta; Anakinra; Canakinumab; Rilonacept; Autoinflammatory syndromes; FAMILIAL MEDITERRANEAN FEVER; COLD AUTOINFLAMMATORY SYNDROME; JUVENILE IDIOPATHIC ARTHRITIS; RECEPTOR ANTAGONIST ANAKINRA; RILONACEPT INTERLEUKIN-1 TRAP; RHEUMATOID-ARTHRITIS; MUCKLE-WELLS; NALP3; INFLAMMASOME; PYOGENIC ARTHRITIS; EFFICACY;
D O I
10.1016/j.ejim.2010.03.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:157 / 163
页数:7
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