β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares

• DOI: 10.1016/j.celrep.2017.02.004
• Publication Date: 2017-03-01T04:14:45Z
• Authors: Emily L. Goldberg; Jennifer L. Asher; Ryan D. Molony; Albert C. Shaw; Caroline J. Zeiss; Chao Wang; Ludmilla A. Moroz...; Raimund I. Herzog; Akiko Iwasaki; Vishwa Deep Dixit
• Keywords: Pyrin domain

Highlights•Inflammation and joint pathology during gout flare is prevented by ketogenic diet•BHB inhibits IL-1β secretion from neutrophils•Ketogenic diet BHB inhibit NLRP3 activation in aged neutrophils•BHB both priming assembly steps of neutrophilsSummaryAging lipotoxicity are two major risk factors for that linked the inflammasome. Neutrophil-mediated production interleukin-1β (IL-1β) drives gouty flares cause destruction, intense pain, fever. However, metabolites impact neutrophil inflammasome remain unknown. Here, we identified (KD) increases β-hydroxybutyrate (BHB) alleviates urate crystal-induced without impairing immune defense against bacterial infection. inhibited S100A9 fibril-primed crystal-activated macrophages, which serve to recruit inflammatory neutrophils joints. Consistent with reduced rats fed a diet, blocked NLRP3-dependent manner mice humans irrespective age. Mechanistically, reducing steps. Collectively, our studies show BHB, known alternate metabolic fuel, also an anti-inflammatory molecule may as treatment gout.Graphical abstract