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beta-Hydroxybutyrate deactivates Neutrophil NLRP3 inflammasome to relieve gout flares
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2017 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 18, no 9, 2077-2087 p.Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
2017. Vol. 18, no 9, 2077-2087 p.
National Category
Cell and Molecular Biology Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-133663DOI: 10.1016/j.celrep.2017.02.004ISI: 000397328400002PubMedID: 28249154OAI: oai:DiVA.org:umu-133663DiVA: diva2:1090794
Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2017-04-25Bibliographically approved

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Wang, ChaoMorozova-Roche, Ludmilla A.
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Department of Medical Biochemistry and Biophysics
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