Service of Rheumatology, Department of Musculoskeletal Medicine, Avenue Pierre Decker 4, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland. alexanderkai-lik.so@ chuv.ch
Nat Rev Rheumatol. 2013 Jul;9(7):391-9. doi: 10.1038/nrrheum.2013.61. Epub 2013 May 14.
Inflammasomes are key inducers of inflammation in response to exogenous and endogenous stimuli, because they regulate the processing and secretion of the proinflammatory cytokines IL-1β and IL-18. Thus, inflammasomes have a crucial role in host defence against infection, but they can also be involved in inflammatory diseases. Indeed, the NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome has been shown to play a part in several inflammatory rheumatic disorders, although the mechanisms involved are better elucidated in some of these diseases than in others. In particular, the pathogenesis of cryopyrin-associated periodic syndromes and microcrystal-induced arthritides is thought to be dependent on activation of the NLRP3 inflammasome, and IL-1 inhibition has shown efficacy as a therapeutic strategy in both groups of conditions. In this Review, we describe the current understanding of the mechanisms that trigger the inflammasome, and consider the relevance of the inflammasome to a variety of rheumatic diseases. In addition, we discuss the current therapies targeting this molecular complex, as well as future therapeutic prospects.
炎症小体是对外源和内源性刺激物产生炎症反应的关键诱导物，因为它们调节促炎细胞因子 IL-1β 和 IL-18 的加工和分泌。因此，炎症小体在宿主抗感染防御中起着至关重要的作用，但它们也可能与炎症性疾病有关。事实上，NLRP3（NOD、LRR 和 pyrin 结构域包含 3）炎症小体已被证明在几种炎症性风湿性疾病中发挥作用，尽管在这些疾病中的一些疾病中比在其他疾病中更好地阐明了涉及的机制。特别是，冷球蛋白血症相关周期性综合征和微晶诱导性关节炎的发病机制被认为依赖于 NLRP3 炎症小体的激活，并且在这两组疾病中，IL-1 抑制已被证明是一种有效的治疗策略。在这篇综述中，我们描述了触发炎症小体的机制的现有认识，并考虑了炎症小体与各种风湿性疾病的相关性。此外，我们还讨论了针对该分子复合物的当前治疗方法以及未来的治疗前景。
