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HSP90 is an intracellular chaperone known to regulate inflammatory processes including the NLRP3 inflammasome and secretion of the pro\u2010inflammatory cytokine interleukin(IL)\u20101\u03b2. Here, primarily using an <jats:italic>in vitro<\/jats:italic> inflammasome ASC speck assay, and an <jats:italic>in vivo<\/jats:italic> model of murine peritonitis, we tested the utility of HSP90 inhibitors as anti\u2010inflammatory molecules. We report that the HSP90 inhibitor EC144 effectively inhibited inflammatory processes including priming and activation of NLRP3 <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. A specific inhibitor of the \u03b2 HSP90 isoform was ineffective suggesting the importance of the \u03b1 isoform in inflammatory signalling. EC144 inhibited IL\u20101\u03b2 and IL\u20106 <jats:italic>in vivo<\/jats:italic> when administered orally, and was brain\u2010penetrant. These data suggest that HSP90 inhibitors may be useful for targeting inflammation in diverse diseases that are worsened by the presence of inflammation.<\/jats:p>","DOI":"10.1111\/imm.13267","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T05:27:22Z","timestamp":1600666042000},"page":"84-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Inhibition of the NLRP3 inflammasome by HSP90 inhibitors"],"prefix":"10.1111","volume":"162","author":[{"given":"Sohaib","family":"Nizami","sequence":"first","affiliation":[{"name":"Alzheimer's Research UK Oxford Drug Discovery Institute University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanisa","family":"Arunasalam","sequence":"additional","affiliation":[{"name":"Alzheimer's Research UK Oxford Drug Discovery Institute University of Oxford Oxford 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