title: Targeting inflammasomes in rheumatic diseases.
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.
authors.affiliation: 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
authors.forename: Alexander
authors.initials: A
authors.lastname: So
authors.forename: Annette
authors.initials: A
authors.lastname: Ives
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
mesh_terms: D002352:Carrier Proteins / Q000502:physiology; D056587:Cryopyrin-Associated Periodic Syndromes / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D058847:Inflammasomes / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology; D020382:Interleukin-18 / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D007375:Interleukin-1; D020382:Interleukin-18; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human