{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:07:49Z","timestamp":1779188869616,"version":"3.51.4"},"reference-count":112,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"University of Vermont Larner College of Medicine and Department of Medicine"},{"DOI":"10.13039\/100000104","name":"U.S. National Aeronautics and Space Administration","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000104","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>NLRP3 inflammasome activation drives interleukin (IL)-1\u03b2 and IL-18 cleavage and secretion and induces pyroptosis. The ketone body \u03b2-hydroxybutyrate (BHB), produced during metabolic stress such as caloric insufficiency, has been reported to inhibit this pathway. However, the conditions that enable this effect, and whether it extends to other short-chain carboxylic acids (SCCAs), are not well defined. Using adenosine triphosphate\u2013stimulated J774 mouse macrophages and human peripheral blood mononuclear cells, we quantified IL-1\u03b2 secretion to determine the pH dependence of BHB and related SCCAs in inhibiting NLRP3 activation. Both enantiomers of \u03b2-hydroxybutyric acid (BHBA) inhibited IL-1\u03b2 secretion, whereas sodium \u03b2-hydroxybutyrate (NaBHB) and sodium hydroxide\u2013neutralized BHBA did not. Acidifying NaBHB stock solutions or the treatment media, or allowing endogenous acidification during cell culture, restored NaBHB\u2019s ability to inhibit NLRP3 activation. Several other 3- to 6-carbon SCCAs also inhibited inflammasome activation in a pH-dependent manner and prevented pyroptotic cell death. Activation of the free fatty acid receptor 3 (GPR41\/FFAR3) both mimicked and enhanced the inhibitory effects of BHBA. Together, these findings demonstrate that acidic conditions enable BHB and multiple SCCAs to suppress NLRP3 inflammasome activation, partly through GPR41\/FFAR3. This expands the set of metabolites that can modulate this key proinflammatory pathway during energetic stress and suggests optimized conditions for the potential therapeutic use of ketone bodies as anti-inflammatory agents.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag085","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:18:26Z","timestamp":1779185906000},"source":"Crossref","is-referenced-by-count":0,"title":["Acidosis enables the NLRP3 inflammasome-inhibiting effects of \u03b2-hydroxybutyrate and short-chain carboxylic acids"],"prefix":"10.1093","volume":"215","author":[{"given":"Madeleine M","family":"Mank","sequence":"first","affiliation":[{"name":"Division of Pulmonary Disease and Critical Care, Vermont Lung Center, Department of Medicine, University of Vermont , Burlington, VT,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlyn A","family":"Zoller","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease and Critical Care, Vermont Lung Center, Department of Medicine, University of Vermont , Burlington, VT,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V Amanda","family":"Fastiggi","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease and Critical Care, Vermont Lung Center, Department of Medicine, University of Vermont , Burlington, VT,","place":["United States"]},{"name":"Cellular, Molecular, and Biomedical Sciences Doctoral Program, University of Vermont , Burlington, VT,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L","family":"Ather","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease and Critical Care, Vermont Lung Center, Department of Medicine, University of Vermont , Burlington, VT,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-4570","authenticated-orcid":false,"given":"Matthew E","family":"Poynter","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Disease and Critical Care, Vermont Lung Center, Department of Medicine, University of Vermont , Burlington, VT,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"2026051906182384500_vkag085-B1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/cr.2015.139","article-title":"Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion","volume":"25","author":"He","year":"2015","journal-title":"Cell Res"},{"key":"2026051906182384500_vkag085-B2","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and regulation of NLRP3 inflammasome activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem Sci"},{"key":"2026051906182384500_vkag085-B3","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.2041-1014.2012.00639.x","article-title":"Tumor necrosis factor-alpha and interleukin-1beta expression pathway induced by Streptococcus mutans in macrophage cell line RAW 264.7","volume":"27","author":"Kim","year":"2012","journal-title":"Mol Oral Microbiol"},{"key":"2026051906182384500_vkag085-B4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00011-012-0555-2","article-title":"Lipopolysaccharide\/adenosine triphosphate-mediated signal transduction in the regulation of NLRP3 protein expression and caspase-1-mediated interleukin-1beta secretion","volume":"62","author":"Liao","year":"2013","journal-title":"Inflamm Res"},{"key":"2026051906182384500_vkag085-B5","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.4049\/jimmunol.149.4.1294","article-title":"IL-1 beta maturation: evidence that mature cytokine formation can be induced specifically by nigericin","volume":"149","author":"Perregaux","year":"1992","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B6","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.4049\/jimmunol.0900164","article-title":"Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity","volume":"183","author":"McKee","year":"2009","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B7","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1126\/science.1156995","article-title":"Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica","volume":"320","author":"Dostert","year":"2008","journal-title":"Science"},{"key":"2026051906182384500_vkag085-B8","doi-asserted-by":"crossref","first-page":"e11765","DOI":"10.1371\/journal.pone.0011765","article-title":"Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation","volume":"5","author":"Rajam\u00e4ki","year":"2010","journal-title":"PLoS One"},{"key":"2026051906182384500_vkag085-B9","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1038\/ni.2749","article-title":"Phosphorylation of the adaptor ASC acts as a molecular switch that controls the formation of speck-like aggregates and inflammasome activity","volume":"14","author":"Hara","year":"2013","journal-title":"Nat Immunol"},{"key":"2026051906182384500_vkag085-B10","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1189\/jlb.3HI0814-371RR","article-title":"Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization","volume":"97","author":"Lin","year":"2015","journal-title":"J Leukoc Biol"},{"key":"2026051906182384500_vkag085-B11","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1002\/smll.201402859","article-title":"NADPH oxidase-dependent NLRP3 inflammasome activation and its important role in lung fibrosis by multiwalled carbon nanotubes","volume":"11","author":"Sun","year":"2015","journal-title":"Small"},{"key":"2026051906182384500_vkag085-B12","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.4049\/jimmunol.0900394","article-title":"NADPH oxidase NOX2 mediates rapid cellular oxidation following ATP stimulation of endotoxin-primed macrophages","volume":"183","author":"Moore","year":"2009","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B13","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.immuni.2012.01.009","article-title":"Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis","volume":"36","author":"Shimada","year":"2012","journal-title":"Immunity"},{"key":"2026051906182384500_vkag085-B14","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat Immunol"},{"key":"2026051906182384500_vkag085-B15","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"2026051906182384500_vkag085-B16","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41419-019-1413-8","article-title":"Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors","volume":"10","author":"Yang","year":"2019","journal-title":"Cell Death Dis"},{"key":"2026051906182384500_vkag085-B17","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1007\/s12010-014-1471-4","article-title":"Purification and analysis of the interactions of caspase-1 and ASC for assembly of the inflammasome","volume":"175","author":"Narayanan","year":"2015","journal-title":"Appl Biochem Biotechnol"},{"key":"2026051906182384500_vkag085-B18","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1042\/BJ20121198","article-title":"The CARD plays a critical role in ASC foci formation and inflammasome signalling","volume":"449","author":"Proell","year":"2013","journal-title":"Biochem J"},{"key":"2026051906182384500_vkag085-B19","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.chom.2012.10.020","article-title":"The Yersinia virulence effector YopM binds caspase-1 to arrest inflammasome assembly and processing","volume":"12","author":"LaRock","year":"2012","journal-title":"Cell Host Microbe"},{"key":"2026051906182384500_vkag085-B20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.cyto.2014.03.007","article-title":"How is inflammation initiated? Individual influences of IL-1, IL-18 and HMGB1","volume":"69","author":"Keyel","year":"2014","journal-title":"Cytokine"},{"key":"2026051906182384500_vkag085-B21","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.4049\/jimmunol.1002720","article-title":"Differential expression of NLRP3 among hematopoietic cells","volume":"186","author":"Guarda","year":"2011","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B22","doi-asserted-by":"crossref","first-page":"e78537","DOI":"10.1371\/journal.pone.0078537","article-title":"Ethanol inhibits activation of NLRP3 and AIM2 inflammasomes in human macrophages\u2014a novel anti-inflammatory action of alcohol","volume":"8","author":"Nurmi","year":"2013","journal-title":"PLoS One"},{"key":"2026051906182384500_vkag085-B23","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/ni.2022","article-title":"Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling","volume":"12","author":"Wen","year":"2011","journal-title":"Nat Immunol"},{"key":"2026051906182384500_vkag085-B24","doi-asserted-by":"crossref","first-page":"15811","DOI":"10.1523\/JNEUROSCI.4088-10.2010","article-title":"The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18","volume":"30","author":"Jha","year":"2010","journal-title":"J Neurosci"},{"key":"2026051906182384500_vkag085-B25","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41392-024-01954-6","article-title":"Metabolic regulation of the immune system in health and diseases: mechanisms and interventions","volume":"9","author":"Hu","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"2026051906182384500_vkag085-B26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-nutr-071816-064916","article-title":"beta-Hydroxybutyrate: a signaling metabolite","volume":"37","author":"Newman","year":"2017","journal-title":"Annu Rev Nutr"},{"key":"2026051906182384500_vkag085-B27","doi-asserted-by":"crossref","first-page":"782","DOI":"10.3390\/nu14040782","article-title":"Molecular mechanisms underlying the bioactive properties of a ketogenic diet","volume":"14","author":"Murakami","year":"2022","journal-title":"Nutrients"},{"key":"2026051906182384500_vkag085-B28","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.diabres.2014.08.009","article-title":"beta-Hydroxybutyrate: much more than a metabolite","volume":"106","author":"Newman","year":"2014","journal-title":"Diabetes Res Clin Pract"},{"key":"2026051906182384500_vkag085-B29","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.tem.2013.09.002","article-title":"Ketone bodies as signaling metabolites","volume":"25","author":"Newman","year":"2014","journal-title":"Trends Endocrinol Metab"},{"key":"2026051906182384500_vkag085-B30","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1038\/oby.2008.678","article-title":"Effects of insulin on ketogenesis following fasting in lean and obese men","volume":"17","author":"Soeters","year":"2009","journal-title":"Obesity (Silver Spring)"},{"key":"2026051906182384500_vkag085-B31","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/(SICI)1520-7560(199911\/12)15:6<412::AID-DMRR72>3.0.CO;2-8","article-title":"Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes","volume":"15","author":"Laffel","year":"1999","journal-title":"Diabetes Metab Res Rev"},{"key":"2026051906182384500_vkag085-B32","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201708712","article-title":"Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last?","volume":"10","author":"Van Wyngene","year":"2018","journal-title":"EMBO Mol Med"},{"key":"2026051906182384500_vkag085-B33","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.tem.2022.01.006","article-title":"Sepsis: a failing starvation response","volume":"33","author":"Vandewalle","year":"2022","journal-title":"Trends Endocrinol Metab"},{"key":"2026051906182384500_vkag085-B34","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1002\/j.2040-4603.2016.tb00693.x","article-title":"Integrative physiology of fasting","volume":"6","author":"Secor","year":"2016","journal-title":"Compr Physiol"},{"key":"2026051906182384500_vkag085-B35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1113\/jphysiol.1980.sp013190","article-title":"Post-exercise ketosis","volume":"301","author":"Koeslag","year":"1980","journal-title":"J Physiol"},{"key":"2026051906182384500_vkag085-B36","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1194\/jlr.R046599","article-title":"Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester","volume":"55","author":"Hashim","year":"2014","journal-title":"J Lipid Res"},{"key":"2026051906182384500_vkag085-B37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.biocel.2015.01.022","article-title":"Mitochondria: the ketogenic diet\u2014a metabolism-based therapy","volume":"63","author":"Vidali","year":"2015","journal-title":"Int J Biochem Cell Biol"},{"key":"2026051906182384500_vkag085-B38","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/jn\/101.12.1719","article-title":"Metabolic fate of 1,3-butanediol in the rat: conversion to -hydroxybutyrate","volume":"101","author":"Tate","year":"1971","journal-title":"J Nutr"},{"key":"2026051906182384500_vkag085-B39","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.expneurol.2007.12.029","article-title":"Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions","volume":"211","author":"Haces","year":"2008","journal-title":"Exp Neurol"},{"key":"2026051906182384500_vkag085-B40","doi-asserted-by":"crossref","first-page":"983401","DOI":"10.1155\/2014\/983401","article-title":"BHBA suppresses LPS-induced inflammation in BV-2 cells by inhibiting NF-kappaB activation","volume":"2014","author":"Fu","year":"2014","journal-title":"Mediators Inflamm"},{"key":"2026051906182384500_vkag085-B41","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/j.celrep.2017.02.004","article-title":"beta-Hydroxybutyrate deactivates neutrophil NLRP3 inflammasome to relieve gout flares","volume":"18","author":"Goldberg","year":"2017","journal-title":"Cell Rep"},{"key":"2026051906182384500_vkag085-B42","doi-asserted-by":"crossref","first-page":"e66522","DOI":"10.7554\/eLife.66522","article-title":"Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice","volume":"10","author":"Ryu","year":"2021","journal-title":"Elife"},{"key":"2026051906182384500_vkag085-B43","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm.3804","article-title":"The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease","volume":"21","author":"Youm","year":"2015","journal-title":"Nat Med"},{"key":"2026051906182384500_vkag085-B44","doi-asserted-by":"crossref","first-page":"702","DOI":"10.5152\/tjg.2021.191062","article-title":"beta-hydroxybutyrate, one of the three main ketone bodies, ameliorates acute pancreatitis in rats by suppressing the NLRP3 inflammasome pathway","volume":"32","author":"Sahin","year":"2021","journal-title":"Turk J Gastroenterol"},{"key":"2026051906182384500_vkag085-B45","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1172\/JCI105650","article-title":"Brain metabolism during fasting","volume":"46","author":"Owen","year":"1967","journal-title":"J Clin Invest"},{"key":"2026051906182384500_vkag085-B46","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/jnc.12975","article-title":"The metabolic impact of beta-hydroxybutyrate on neurotransmission: Reduced glycolysis mediates changes in calcium responses and KATP channel receptor sensitivity","volume":"132","author":"Lund","year":"2015","journal-title":"J Neurochem"},{"key":"2026051906182384500_vkag085-B47","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12986-016-0069-y","article-title":"Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats","volume":"13","author":"Kesl","year":"2016","journal-title":"Nutr Metab (Lond)"},{"key":"2026051906182384500_vkag085-B48","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cmet.2016.07.010","article-title":"Nutritional ketosis alters fuel preference and thereby endurance performance in athletes","volume":"24","author":"Cox","year":"2016","journal-title":"Cell Metab"},{"key":"2026051906182384500_vkag085-B49","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1113\/JP280955","article-title":"Lactate in contemporary biology: a phoenix risen","volume":"600","author":"Brooks","year":"2022","journal-title":"J Physiol"},{"key":"2026051906182384500_vkag085-B50","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.4049\/jimmunol.0902584","article-title":"Lactic acid and acidification inhibit TNF secretion and glycolysis of human monocytes","volume":"184","author":"Dietl","year":"2010","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B51","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.3389\/fimmu.2018.02564","article-title":"In vitro and in vivo effects of lactate on metabolism and cytokine production of human primary PBMCs and monocytes","volume":"9","author":"Ratter","year":"2018","journal-title":"Front Immunol"},{"key":"2026051906182384500_vkag085-B52","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/08830185.2021.1955876","article-title":"Lactic acid in macrophage polarization: the significant role in inflammation and cancer","volume":"41","author":"Zhou","year":"2022","journal-title":"Int Rev Immunol"},{"key":"2026051906182384500_vkag085-B53","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.metabol.2015.10.001","article-title":"Anti-inflammatory effects of the hydroxycarboxylic acid receptor 2","volume":"65","author":"Graff","year":"2016","journal-title":"Metabolism"},{"key":"2026051906182384500_vkag085-B54","doi-asserted-by":"crossref","first-page":"8030","DOI":"10.1073\/pnas.1016088108","article-title":"Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41)","volume":"108","author":"Kimura","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026051906182384500_vkag085-B55","doi-asserted-by":"crossref","first-page":"5364","DOI":"10.1038\/s41467-024-49536-y","article-title":"Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode","volume":"15","author":"Shenol","year":"2024","journal-title":"Nat Commun"},{"key":"2026051906182384500_vkag085-B56","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.4049\/jimmunol.1600406","article-title":"Ethanol and other short-chain alcohols inhibit NLRP3 inflammasome activation through protein tyrosine phosphatase stimulation","volume":"197","author":"Hoyt","year":"2016","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B57","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jacig.2022.08.001","article-title":"Ketone body augmentation decreases methacholine hyperresponsiveness in mouse models of allergic asthma","volume":"1","author":"Mank","year":"2022","journal-title":"J Allergy Clin Immunol Glob"},{"key":"2026051906182384500_vkag085-B58","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.4049\/jimmunol.165.8.4615","article-title":"ATP acts as an agonist to promote stimulus-induced secretion of IL-1 beta and IL-18 in human blood","volume":"165","author":"Perregaux","year":"2000","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B59","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.1016\/S0021-9258(19)63335-1","article-title":"Utilization of L(+)-3-hydroxybutyrate, D(-)-3-hydroxybutyrate, acetoacetate, and glucose for respiration and lipid synthesis in the 18-day-old rat","volume":"252","author":"Webber","year":"1977","journal-title":"J Biol Chem"},{"key":"2026051906182384500_vkag085-B60","doi-asserted-by":"crossref","first-page":"805881","DOI":"10.3389\/fimmu.2022.805881","article-title":"Beta-hydroxybutyrate: a dual function molecular and immunological barrier function regulator","volume":"13","author":"Qi","year":"2022","journal-title":"Front Immunol"},{"key":"2026051906182384500_vkag085-B61","doi-asserted-by":"crossref","first-page":"e2400426","DOI":"10.1002\/advs.202400426","article-title":"Adaptive metabolic responses facilitate blood-brain barrier repair in ischemic stroke via BHB-mediated epigenetic modification of ZO-1 expression","volume":"11","author":"Li","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"2026051906182384500_vkag085-B62","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj3430281","article-title":"The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation","volume":"343 Pt 2","author":"Halestrap","year":"1999","journal-title":"Biochem J"},{"key":"2026051906182384500_vkag085-B63","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.cmet.2016.12.022","article-title":"Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics","volume":"25","author":"Puchalska","year":"2017","journal-title":"Cell Metab"},{"key":"2026051906182384500_vkag085-B64","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-nutr-111120-111518","article-title":"Metabolic and signaling roles of ketone bodies in health and disease","volume":"41","author":"Puchalska","year":"2021","journal-title":"Annu Rev Nutr"},{"key":"2026051906182384500_vkag085-B65","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.jhep.2018.04.004","article-title":"beta-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway","volume":"69","author":"Chen","year":"2018","journal-title":"J Hepatol"},{"key":"2026051906182384500_vkag085-B66","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1021\/jm800896z","article-title":"Nicotinic acid receptor agonists","volume":"51","author":"Boatman","year":"2008","journal-title":"J Med Chem"},{"key":"2026051906182384500_vkag085-B67","doi-asserted-by":"crossref","first-page":"19314","DOI":"10.1523\/JNEUROSCI.3102-13.2013","article-title":"beta-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3","volume":"33","author":"Won","year":"2013","journal-title":"J Neurosci"},{"key":"2026051906182384500_vkag085-B68","doi-asserted-by":"crossref","first-page":"111437","DOI":"10.1016\/j.celrep.2022.111437","article-title":"The ketone body beta-hydroxybutyrate mitigates ILC2-driven airway inflammation by regulating mast cell function","volume":"40","author":"Thio","year":"2022","journal-title":"Cell Rep"},{"key":"2026051906182384500_vkag085-B69","doi-asserted-by":"crossref","first-page":"1127845","DOI":"10.3389\/fnut.2023.1127845","article-title":"Ketogenic diet alleviates renal fibrosis in mice by enhancing fatty acid oxidation through the free fatty acid receptor 3 pathway","volume":"10","author":"Qiu","year":"2023","journal-title":"Front Nutr"},{"key":"2026051906182384500_vkag085-B70","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev-nutr-120919-094440","article-title":"Nutrition regulates innate immunity in health and disease","volume":"40","author":"Nobs","year":"2020","journal-title":"Annu Rev Nutr"},{"key":"2026051906182384500_vkag085-B71","doi-asserted-by":"crossref","first-page":"e20221839","DOI":"10.1084\/jem.20221839","article-title":"Nutrients: signal 4 in T cell immunity","volume":"221","author":"Raynor","year":"2024","journal-title":"J Exp Med"},{"key":"2026051906182384500_vkag085-B72","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.it.2023.06.002","article-title":"Physiological role of cytokines in the regulation of mammalian metabolism","volume":"44","author":"de Baat","year":"2023","journal-title":"Trends Immunol"},{"key":"2026051906182384500_vkag085-B73","first-page":"218","article-title":"Pathways for cytokine secretion","volume":"25","author":"Stanley","year":"2010","journal-title":"Physiology (Bethesda)"},{"key":"2026051906182384500_vkag085-B74","doi-asserted-by":"crossref","first-page":"C707","DOI":"10.1152\/ajpcell.00478.2023","article-title":"Ketone bodies as chemical signals for the immune system","volume":"326","author":"Gonzatti","year":"2024","journal-title":"Am J Physiol Cell Physiol"},{"key":"2026051906182384500_vkag085-B75","first-page":"167","article-title":"Emerging pathophysiological roles of ketone bodies","volume":"39","author":"Tsuruta","year":"2024","journal-title":"Physiology (Bethesda)"},{"key":"2026051906182384500_vkag085-B76","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1113\/EP090430","article-title":"Exogenous ketone supplementation: an emerging tool for physiologists with potential as a metabolic therapy","volume":"108","author":"Falkenhain","year":"2023","journal-title":"Exp Physiol"},{"key":"2026051906182384500_vkag085-B77","author":"Ghimire"},{"key":"2026051906182384500_vkag085-B78","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1056\/NEJMc052709","article-title":"Ketoacidosis during a low-carbohydrate diet","volume":"354","author":"Shah","year":"2006","journal-title":"N Engl J Med"},{"key":"2026051906182384500_vkag085-B79","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/S0140-6736(21)00536-5","article-title":"SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications","volume":"398","author":"Brown","year":"2021","journal-title":"Lancet"},{"key":"2026051906182384500_vkag085-B80","doi-asserted-by":"crossref","first-page":"156035","DOI":"10.1016\/j.metabol.2024.156035","article-title":"Starvation and infection: The role of sickness-associated anorexia in metabolic adaptation during acute infection","volume":"161","author":"Jindal","year":"2024","journal-title":"Metabolism"},{"key":"2026051906182384500_vkag085-B81","doi-asserted-by":"crossref","first-page":"10591","DOI":"10.1038\/s41598-022-14961-w","article-title":"Efficacy and safety of ketone ester infusion to prevent muscle weakness in a mouse model of sepsis-induced critical illness","volume":"12","author":"Weckx","year":"2022","journal-title":"Sci Rep"},{"key":"2026051906182384500_vkag085-B82","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/s41586-022-05128-8","article-title":"Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19","volume":"609","author":"Karagiannis","year":"2022","journal-title":"Nature"},{"key":"2026051906182384500_vkag085-B83","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1016\/j.immuni.2023.07.002","article-title":"Ketolysis drives CD8(+) T cell effector function through effects on histone acetylation","volume":"56","author":"Luda","year":"2023","journal-title":"Immunity"},{"key":"2026051906182384500_vkag085-B84","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s42255-019-0160-6","article-title":"Ketogenesis activates metabolically protective gammadelta T cells in visceral adipose tissue","volume":"2","author":"Goldberg","year":"2020","journal-title":"Nat Metab"},{"key":"2026051906182384500_vkag085-B85","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.medj.2020.06.008","article-title":"Investigating ketone bodies as immunometabolic countermeasures against respiratory viral infections","volume":"1","author":"Stubbs","year":"2020","journal-title":"Med"},{"key":"2026051906182384500_vkag085-B86","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.sapharm.2024.04.015","article-title":"Oral beta-hydroxybutyrate alleviates COVID-19 related acute respiratory distress syndrome: a randomized, single-blind, placebo-controlled trial","volume":"20","author":"Shahtaghi","year":"2024","journal-title":"Res Social Adm Pharm"},{"key":"2026051906182384500_vkag085-B87","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/j.cmet.2023.09.001","article-title":"Ketogenesis promotes tolerance to Pseudomonas aeruginosa pulmonary infection","volume":"35","author":"Tomlinson","year":"2023","journal-title":"Cell Metab"},{"key":"2026051906182384500_vkag085-B88","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.3390\/nu16223957","article-title":"Low-dose ketone monoester administration in adults with cystic fibrosis: a pilot and feasibility study","volume":"16","author":"Plaisance","year":"2024","journal-title":"Nutrients"},{"key":"2026051906182384500_vkag085-B89","doi-asserted-by":"crossref","first-page":"L243","DOI":"10.1152\/ajplung.00309.2021","article-title":"Therapeutic ketosis decreases methacholine hyperresponsiveness in mouse models of inherent obese asthma","volume":"322","author":"Mank","year":"2022","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026051906182384500_vkag085-B90","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4049\/jimmunol.2200267","article-title":"Suppression of experimental autoimmune encephalomyelitis in mice by beta-hydroxy beta-methylbutyrate, a body-building supplement in humans","volume":"211","author":"Sheinin","year":"2023","journal-title":"J Immunol"},{"key":"2026051906182384500_vkag085-B91","doi-asserted-by":"crossref","first-page":"114891","DOI":"10.1016\/j.celrep.2024.114891","article-title":"A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity","volume":"43","author":"Alexander","year":"2024","journal-title":"Cell Rep"},{"key":"2026051906182384500_vkag085-B92","first-page":"677","article-title":"Salt-responsive metabolite, beta-hydroxybutyrate","volume":"25","author":"Chakraborty","year":"2018","journal-title":"Attenuates Hypertension. Cell Rep"},{"key":"2026051906182384500_vkag085-B93","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1042\/BCJ20230403","article-title":"Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice","volume":"481","author":"Bass","year":"2024","journal-title":"Biochem J"},{"key":"2026051906182384500_vkag085-B94","doi-asserted-by":"crossref","first-page":"e70027","DOI":"10.1096\/fj.202401188R","article-title":"Preconditioning with beta-hydroxybutyrate attenuates lung ischemia-reperfusion injury by suppressing alveolar macrophage pyroptosis through the SIRT1-FOXO3 signaling pathway","volume":"38","author":"Lu","year":"2024","journal-title":"Faseb J"},{"key":"2026051906182384500_vkag085-B95","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1016\/j.clnu.2024.06.036","article-title":"Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: a randomized clinical trial","volume":"43","author":"Guevara-Cruz","year":"2024","journal-title":"Clin Nutr"},{"key":"2026051906182384500_vkag085-B96","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1111\/j.1471-4159.1986.tb00695.x","article-title":"Comparative stereostructure-activity studies on GABAA and GABAB receptor sites and GABA uptake using rat brain membrane preparations","volume":"47","author":"Falch","year":"1986","journal-title":"J Neurochem"},{"key":"2026051906182384500_vkag085-B97","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.tibs.2019.01.005","article-title":"Ketoacidosis - where do the protons come from?","volume":"44","author":"Green","year":"2019","journal-title":"Trends Biochem Sci"},{"key":"2026051906182384500_vkag085-B98","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3390\/metabo13070803","article-title":"The computational acid-base chemistry of hepatic ketoacidosis","volume":"13","author":"Torrens","year":"2023","journal-title":"Metabolites"},{"key":"2026051906182384500_vkag085-B99","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.cell.2017.03.023","article-title":"Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase","volume":"169","author":"Cantor","year":"2017","journal-title":"Cell"},{"key":"2026051906182384500_vkag085-B100","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1136\/bmjnph-2023-000672","article-title":"Evaluation of the safety and tolerability of exogenous ketosis induced by orally administered free beta-hydroxybutyrate in healthy adult subjects","volume":"6","author":"Pimentel-Suarez","year":"2023","journal-title":"BMJ Nutr Prev Health"},{"key":"2026051906182384500_vkag085-B101","doi-asserted-by":"crossref","first-page":"848","DOI":"10.3389\/fphys.2017.00848","article-title":"On the metabolism of exogenous ketones in humans","volume":"8","author":"Stubbs","year":"2017","journal-title":"Front Physiol"},{"key":"2026051906182384500_vkag085-B102","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nm.3806","article-title":"A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases","volume":"21","author":"Coll","year":"2015","journal-title":"Nat Med"},{"key":"2026051906182384500_vkag085-B103","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41590-020-0669-6","article-title":"FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation","volume":"21","author":"Hu","year":"2020","journal-title":"Nat Immunol"},{"key":"2026051906182384500_vkag085-B104","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.4110\/in.2023.23.e23","article-title":"Extracellular acidification augments NLRP3-mediated inflammasome signaling in macrophages","volume":"23","author":"Chae","year":"2023","journal-title":"Immune Netw"},{"key":"2026051906182384500_vkag085-B105","doi-asserted-by":"crossref","first-page":"30485","DOI":"10.1074\/jbc.M113.478941","article-title":"Acidosis drives damage-associated molecular pattern (DAMP)-induced interleukin-1 secretion via a caspase-1-independent pathway","volume":"288","author":"Edye","year":"2013","journal-title":"J Biol Chem"},{"key":"2026051906182384500_vkag085-B106","doi-asserted-by":"crossref","first-page":"13410","DOI":"10.1074\/jbc.M112.426254","article-title":"Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome","volume":"288","author":"Rajam\u00e4ki","year":"2013","journal-title":"J Biol Chem"},{"key":"2026051906182384500_vkag085-B107","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1126\/science.1227166","article-title":"Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor","volume":"339","author":"Shimazu","year":"2013","journal-title":"Science"},{"key":"2026051906182384500_vkag085-B108","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.molcel.2016.03.036","article-title":"Metabolic regulation of gene expression by histone lysine beta-hydroxybutyrylation","volume":"62","author":"Xie","year":"2016","journal-title":"Mol Cell"},{"key":"2026051906182384500_vkag085-B109","doi-asserted-by":"crossref","first-page":"110044","DOI":"10.1016\/j.celrep.2021.110044","article-title":"Reprogramming of H3K9bhb at regulatory elements is a key feature of fasting in the small intestine","volume":"37","author":"Terranova","year":"2021","journal-title":"Cell Rep"},{"key":"2026051906182384500_vkag085-B110","doi-asserted-by":"crossref","first-page":"109487","DOI":"10.1016\/j.celrep.2021.109487","article-title":"Ketogenesis impact on liver metabolism revealed by proteomics of lysine beta-hydroxybutyrylation","volume":"36","author":"Koronowski","year":"2021","journal-title":"Cell Rep"},{"key":"2026051906182384500_vkag085-B111","doi-asserted-by":"crossref","first-page":"eabe2771","DOI":"10.1126\/sciadv.abe2771","article-title":"The regulatory enzymes and protein substrates for the lysine beta-hydroxybutyrylation pathway","volume":"7","author":"Huang","year":"2021","journal-title":"Sci Adv"},{"key":"2026051906182384500_vkag085-B112","doi-asserted-by":"crossref","first-page":"107235","DOI":"10.1016\/j.isci.2023.107235","article-title":"Non-specific recognition of histone modifications by H3K9bhb antibody","volume":"26","author":"Tsusaka","year":"2023","journal-title":"iScience"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/5\/vkag085\/68334230\/vkag085.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/215\/5\/vkag085\/68334230\/vkag085.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:18:39Z","timestamp":1779185919000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/doi\/10.1093\/jimmun\/vkag085\/8687293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":112,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,14]]}},"URL":"https:\/\/doi.org\/10.1093\/jimmun\/vkag085","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,5]]},"article-number":"vkag085"}}