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  • Review Article
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Targeting inflammasomes in rheumatic diseases

Nature Reviews Rheumatology volume 9, pages 391–399 (2013)Cite this article

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Abstract

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.

Key Points

  • Inflammasomes are the principal mediators of IL-1β and IL-18 release by monocytes and macrophages

  • Inflammasomes are activated by a large number of cellular factors, such as calcium, potassium efflux, reactive oxygen species and ATP; this list continues to expand

  • A link between inflammasome activation and disease has been clearly established for cryopyrin-associated periodic syndromes and microcrystal-induced arthritides such as gout and basic calcium phosphate-induced calcific tendinitis

  • Several inflammatory rheumatic diseases respond to IL-1 inhibitors, which suggests that dysregulation of IL-1β production might be pathogenic

  • IL-1 inhibitors have been the main treatment for inflammasome-mediated diseases, but there might be other pathways that can be targeted therapeutically

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Figure 1: Priming the inflammasome.
Figure 2: Mechanisms of inflammasome activation.

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Acknowledgements

We acknowledge the support of the Swiss National Science Foundation (Grant 310030_130085), the Fondation Warnery and the Institute of Arthritis Research.

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Authors and Affiliations

  1. Department of Musculoskeletal Medicine, Service of Rheumatology, Avenue Pierre Decker 4, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011, Lausanne, Switzerland

    Alexander So, Annette Ives & Nathalie Busso

  2. Department of Medicine, Radboud University Nijmegen Medical Centre and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Geert Grooteplein zuid 8, Nijmegen, 6525 GA, The Netherlands

    Leo A. B. Joosten

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A. So contributed to researching data for the article, discussions of content, writing the article and reviewing/editing the manuscript. A. Ives and N. Busso contributed to researching data for the article, writing the article and reviewing/editing the manuscript. L. A. B. Joosten contributed to discussions of content and writing the article.

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Correspondence to Alexander So.

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A. So has received honoraria from Novartis AG for participation in advisory boards and consultant fees. The other authors declare no competing interests.

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So, A., Ives, A., Joosten, L. et al. Targeting inflammasomes in rheumatic diseases. Nat Rev Rheumatol 9, 391–399 (2013). https://doi.org/10.1038/nrrheum.2013.61

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