{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:39:40Z","timestamp":1790300380882,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Tri-Service General Hospital Songshan Branch, Taiwan"},{"name":"Ministry of National Defense-Medical Affairs Bureau, Taiwan"},{"name":"MacKay Memorial Hospital, Taiwan"},{"name":"Tri-Service General Hospital Keelung Branch, Taiwan"},{"name":"Ministry of Science and Technology, Taiwan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflamm. Res."],"DOI":"10.1007\/s00011-026-02290-x","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:33:44Z","timestamp":1781188424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactate acts as a metabolic brake on inflammation by repressing NLRP3 transcription via NF-\u03baB inhibition"],"prefix":"10.1007","volume":"75","author":[{"given":"Hsin-An","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Chung","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yung","family":"Chiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Hsuan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Ying","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuen-Jou","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Feng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Tien","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-I.","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Yang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lih-Chyang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"2290_CR1","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","volume":"19","author":"KV Swanson","year":"2019","unstructured":"Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19:477\u201389.","journal-title":"Nat Rev Immunol"},{"key":"2290_CR2","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.immuni.2006.02.004","volume":"24","author":"FS Sutterwala","year":"2006","unstructured":"Sutterwala FS, Ogura Y, Szczepanik M, Lara-Tejero M, Lichtenberger GS, Grant EP, et al. Critical role for NALP3\/CIAS1\/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1. Immunity. 2006;24:317\u201327.","journal-title":"Immunity"},{"key":"2290_CR3","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1164\/rccm.201604-0892OC","volume":"196","author":"S Lee","year":"2017","unstructured":"Lee S, Nakahira K, Dalli J, Siempos II, Norris PC, Colas RA, et al. NLRP3 inflammasome deficiency protects against microbial sepsis via increased Lipoxin B4 synthesis. Am J Respir Crit Care Med. 2017;196:713\u201326.","journal-title":"Am J Respir Crit Care Med"},{"key":"2290_CR4","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature04516","volume":"440","author":"F Martinon","year":"2006","unstructured":"Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237\u201341.","journal-title":"Nature"},{"key":"2290_CR5","doi-asserted-by":"publisher","first-page":"194","DOI":"10.2337\/db12-0420","volume":"62","author":"HM Lee","year":"2013","unstructured":"Lee HM, Kim JJ, Kim HJ, Shong M, Ku BJ, Jo EK. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes. 2013;62:194\u2013204.","journal-title":"Diabetes"},{"key":"2290_CR6","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/nature11729","volume":"493","author":"MT Heneka","year":"2013","unstructured":"Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, et al. NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice. Nature. 2013;493:674\u20138.","journal-title":"Nature"},{"key":"2290_CR7","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/nature04515","volume":"440","author":"S Mariathasan","year":"2006","unstructured":"Mariathasan S, Weiss DS, Newton K, McBride J, O\u2019Rourke K, Roose-Girma M, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006;440:228\u201332.","journal-title":"Nature"},{"key":"2290_CR8","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.immuni.2013.05.016","volume":"38","author":"R Munoz-Planillo","year":"2013","unstructured":"Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM, Nunez G. K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 2013;38:1142\u201353.","journal-title":"Immunity"},{"key":"2290_CR9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20151570","volume":"213","author":"LA O'Neill","year":"2016","unstructured":"O\u2019Neill LA, Pearce EJ. Immunometabolism governs dendritic cell and macrophage function. J Exp Med. 2016;213:15\u201323.","journal-title":"J Exp Med"},{"key":"2290_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110489","volume":"38","author":"I Cobo","year":"2022","unstructured":"Cobo I, Cheng A, Murillo-Saich J, Coras R, Torres A, Abe Y, et al. Monosodium urate crystals regulate a unique JNK-dependent macrophage metabolic and inflammatory response. Cell Rep. 2022;38:110489.","journal-title":"Cell Rep"},{"key":"2290_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13280","volume":"7","author":"M Xie","year":"2016","unstructured":"Xie M, Yu Y, Kang R, Zhu S, Yang L, Zeng L, et al. PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nat Commun. 2016;7:13280.","journal-title":"Nat Commun"},{"key":"2290_CR12","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1111\/imm.13628","volume":"169","author":"LC Chen","year":"2023","unstructured":"Chen LC, Chen YJ, Lin HA, Chien WC, Tsai KJ, Chung CH, et al. Inactivation of mitochondrial pyruvate carrier promotes NLRP3 inflammasome activation and gout development via metabolic reprogramming. Immunology. 2023;169:271\u201391.","journal-title":"Immunology"},{"key":"2290_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.630380","volume":"12","author":"HC Lin","year":"2021","unstructured":"Lin HC, Chen YJ, Wei YH, Lin HA, Chen CC, Liu TF, et al. Lactic acid fermentation is required for NLRP3 inflammasome activation. Front Immunol. 2021;12:630380.","journal-title":"Front Immunol"},{"key":"2290_CR14","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1152\/jappl.1978.44.3.350","volume":"44","author":"L Jorfeldt","year":"1978","unstructured":"Jorfeldt L, Juhlin-Dannfelt A, Karlsson J. Lactate release in relation to tissue lactate in human skeletal muscle during exercise. J Appl Physiol. 1978;44:350\u20132.","journal-title":"J Appl Physiol"},{"key":"2290_CR15","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1097\/SHK.0b013e318254d41a","volume":"38","author":"P Wacharasint","year":"2012","unstructured":"Wacharasint P, Nakada TA, Boyd JH, Russell JA, Walley KR. Normal-range blood lactate concentration in septic shock is prognostic and predictive. Shock. 2012;38:4\u201310.","journal-title":"Shock"},{"key":"2290_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002202","volume":"13","author":"R Haas","year":"2015","unstructured":"Haas R, Smith J, Rocher-Ros V, Nadkarni S, Montero-Melendez T, D\u2019Acquisto F, et al. Lactate regulates metabolic and pro-inflammatory circuits in control of T cell migration and effector functions. PLoS Biol. 2015;13:e1002202.","journal-title":"PLoS Biol"},{"key":"2290_CR17","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1007\/s00134-015-4127-0","volume":"42","author":"SA Haas","year":"2016","unstructured":"Haas SA, Lange T, Saugel B, Petzoldt M, Fuhrmann V, Metschke M, et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Med. 2016;42:202\u201310.","journal-title":"Intensive Care Med"},{"key":"2290_CR18","first-page":"916","volume":"60","author":"S Walenta","year":"2000","unstructured":"Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfor K, Rofstad EK, et al. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res. 2000;60:916\u201321.","journal-title":"Cancer Res"},{"key":"2290_CR19","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s11739-020-02337-9","volume":"16","author":"A Gharipour","year":"2021","unstructured":"Gharipour A, Razavi R, Gharipour M, Modarres R, Nezafati P, Mirkheshti N. The incidence and outcome of severe hyperlactatemia in critically ill patients. Intern Emerg Med. 2021;16:115\u201323.","journal-title":"Intern Emerg Med"},{"key":"2290_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107451","volume":"206","author":"TP Brown","year":"2020","unstructured":"Brown TP, Ganapathy V. Lactate\/GPR81 signaling and proton motive force in cancer: role in angiogenesis, immune escape, nutrition, and Warburg phenomenon. Pharmacol Ther. 2020;206:107451.","journal-title":"Pharmacol Ther"},{"key":"2290_CR21","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-019-1678-1","volume":"574","author":"D Zhang","year":"2019","unstructured":"Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574:575\u201380.","journal-title":"Nature"},{"key":"2290_CR22","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/s41392-022-01151-3","volume":"7","author":"X Li","year":"2022","unstructured":"Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, et al. Lactate metabolism in human health and disease. Signal Transduct Target Ther. 2022;7:305.","journal-title":"Signal Transduct Target Ther"},{"key":"2290_CR23","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1016\/j.molcel.2022.06.030","volume":"82","author":"C Torrini","year":"2022","unstructured":"Torrini C, Nguyen TTT, Shu C, Mela A, Humala N, Mahajan A, et al. Lactate is an epigenetic metabolite that drives survival in model systems of glioblastoma. Mol Cell. 2022;82:3061-3076 e6.","journal-title":"Mol Cell"},{"key":"2290_CR24","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1038\/s41467-025-58563-2","volume":"16","author":"H Cai","year":"2025","unstructured":"Cai H, Chen X, Liu Y, Chen Y, Zhong G, Chen X, et al. Lactate activates trained immunity by fueling the tricarboxylic acid cycle and regulating histone lactylation. Nat Commun. 2025;16:3230.","journal-title":"Nat Commun"},{"key":"2290_CR25","doi-asserted-by":"publisher","first-page":"2992","DOI":"10.1016\/j.cell.2025.03.048","volume":"188","author":"A Ziogas","year":"2025","unstructured":"Ziogas A, Novakovic B, Ventriglia L, Galang N, Tran KA, Li W, et al. Long-term histone lactylation connects metabolic and epigenetic rewiring in innate immune memory. Cell. 2025;188:2992-3012 e16.","journal-title":"Cell"},{"key":"2290_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21145104","author":"HC Lin","year":"2020","unstructured":"Lin HC, Chen YJ, Wei YH, Chuang YT, Hsieh SH, Hsieh JY, et al. Cbl negatively regulates NLRP3 inflammasome activation through GLUT1-dependent glycolysis inhibition. Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21145104.","journal-title":"Int J Mol Sci"},{"key":"2290_CR27","doi-asserted-by":"publisher","first-page":"455","DOI":"10.4049\/jimmunol.1401110","volume":"194","author":"DP Sester","year":"2015","unstructured":"Sester DP, Thygesen SJ, Sagulenko V, Vajjhala PR, Cridland JA, Vitak N, et al. A novel flow cytometric method to assess inflammasome formation. J Immunol. 2015;194:455\u201362.","journal-title":"J Immunol"},{"key":"2290_CR28","doi-asserted-by":"publisher","DOI":"10.3390\/nu11030516","author":"IC Chung","year":"2019","unstructured":"Chung IC, OuYang CN, Yuan SN, Lin HC, Huang KY, Wu PS, et al. Pretreatment with a heat-killed probiotic modulates the NLRP3 inflammasome and attenuates colitis-associated colorectal cancer in mice. Nutrients. 2019. https:\/\/doi.org\/10.3390\/nu11030516.","journal-title":"Nutrients"},{"key":"2290_CR29","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.celrep.2015.05.046","volume":"12","author":"JS Moon","year":"2015","unstructured":"Moon JS, Hisata S, Park MA, DeNicola GM, Ryter SW, Nakahira K, et al. mTORC1-induced HK1-dependent glycolysis regulates NLRP3 inflammasome activation. Cell Rep. 2015;12:102\u201315.","journal-title":"Cell Rep"},{"key":"2290_CR30","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/ni.3659","volume":"18","author":"E Dror","year":"2017","unstructured":"Dror E, Dalmas E, Meier DT, Wueest S, Thevenet J, Thienel C, et al. Postprandial macrophage-derived IL-1beta stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol. 2017;18:283\u201392.","journal-title":"Nat Immunol"},{"key":"2290_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-026-08708-y","author":"HA Lin","year":"2026","unstructured":"Lin HA, Lin HC, Tsai MH, Chen YJ, Bao BY, Tsai KJ, et al. Lactic acid drives NLRP3 inflammasome activation and caspase-1-like cytokine cleavage via intracellular acidification. Cell Death Dis. 2026. https:\/\/doi.org\/10.1038\/s41419-026-08708-y.","journal-title":"Cell Death Dis"},{"key":"2290_CR32","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1053\/j.gastro.2014.03.014","volume":"146","author":"R Hoque","year":"2014","unstructured":"Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. Gastroenterology. 2014;146:1763\u201374.","journal-title":"Gastroenterology"},{"key":"2290_CR33","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature09663","volume":"469","author":"R Zhou","year":"2011","unstructured":"Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221\u20135.","journal-title":"Nature"},{"key":"2290_CR34","doi-asserted-by":"publisher","first-page":"787","DOI":"10.4049\/jimmunol.0901363","volume":"183","author":"FG Bauernfeind","year":"2009","unstructured":"Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol. 2009;183:787\u201391.","journal-title":"J Immunol"},{"key":"2290_CR35","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.febslet.2012.02.045","volume":"586","author":"Y Qiao","year":"2012","unstructured":"Qiao Y, Wang P, Qi J, Zhang L, Gao C. TLR-induced NF-kappaB activation regulates NLRP3 expression in murine macrophages. FEBS Lett. 2012;586:1022\u20136.","journal-title":"FEBS Lett"},{"key":"2290_CR36","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1146\/annurev.immunol.18.1.621","volume":"18","author":"M Karin","year":"2000","unstructured":"Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity. Annu Rev Immunol. 2000;18:621\u201363.","journal-title":"Annu Rev Immunol"},{"key":"2290_CR37","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1111\/imm.70075","volume":"177","author":"Y Yang","year":"2026","unstructured":"Yang Y, Zhang Y, Liu K, Zhang H, Zuo X, Guo M. Lactate and lactylation in immune cell function and autoimmune diseases: mechanisms and therapeutic potential. Immunology. 2026;177:643\u201361.","journal-title":"Immunology"},{"key":"2290_CR38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.587913","volume":"11","author":"K Yang","year":"2020","unstructured":"Yang K, Xu J, Fan M, Tu F, Wang X, Ha T, et al. Lactate suppresses macrophage pro-inflammatory response to LPS stimulation by inhibition of YAP and NF-kappaB activation via GPR81-mediated signaling. Front Immunol. 2020;11:587913.","journal-title":"Front Immunol"},{"key":"2290_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163694","volume":"11","author":"A Errea","year":"2016","unstructured":"Errea A, Cayet D, Marchetti P, Tang C, Kluza J, Offermanns S, et al. Lactate inhibits the pro-inflammatory response and metabolic reprogramming in murine macrophages in a GPR81-independent manner. PLoS ONE. 2016;11:e0163694.","journal-title":"PLoS ONE"},{"key":"2290_CR40","doi-asserted-by":"publisher","first-page":"13410","DOI":"10.1074\/jbc.M112.426254","volume":"288","author":"K Rajamaki","year":"2013","unstructured":"Rajamaki K, Nordstrom T, Nurmi K, Akerman KE, Kovanen PT, Oorni K, et al. Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome. J Biol Chem. 2013;288:13410\u20139.","journal-title":"J Biol Chem"}],"container-title":["Inflammation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-026-02290-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00011-026-02290-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-026-02290-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:33:46Z","timestamp":1781188426000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00011-026-02290-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2290"],"URL":"https:\/\/doi.org\/10.1007\/s00011-026-02290-x","relation":{},"ISSN":["1420-908X"],"issn-type":[{"value":"1420-908X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]},"assertion":[{"value":"4 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study was conducted in compliance with the ethical approval of the Institutional Animal Care and Use Committee (IACUC) of MacKay Medical University (approval number: A1090020(m)-6).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All the authors have read the manuscript and agreed to submit the paper to the journal.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"137"}}