{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T17:15:20Z","timestamp":1794071720103,"version":"4.8.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The role of neutrophils in exertional heat stroke (EHS), a life-threatening condition characterized by systemic inflammation, remains poorly defined. This study aimed to characterize the longitudinal profiles of neutrophil recruitment and activation in EHS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective study with a small sample size, we analyzed clinical data and biobanked serum samples from 18 EHS patients and 18 matched healthy controls. Serum levels of interleukin-6 (IL-6), IL-8, IL-17, granulocyte colony-stimulating factor (G-CSF), CXCL1, CXCL2, C-reactive protein (CRP), serum amyloid A (SAA), myeloperoxidase (MPO), and neutrophil elastase (NE) were quantified by ELISA at onset and on days 3, 5, and 7 post-treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At onset, EHS patients exhibited significant neutrophilia and elevated levels of IL-8, CXCL1, CXCL2, and IL-17 (all P &amp;lt; 0.05). While neutrophil counts normalized within days post-treatment, MPO and NE levels remained persistently and significantly elevated throughout the 7-day follow-up compared to controls (all P &amp;lt; 0.0001). Furthermore, strong positive correlations were observed between the levels of CXCL1\/CXCL2 and MPO\/NE at disease onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this exploratory study, our findings reveal a dissociation between neutrophil recruitment and activation in EHS. The persistent elevation of MPO and NE long after count normalization suggests a prolonged state of neutrophil dysregulation that could contribute to both acute tissue injury and long-term immune complications in EHS survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1718617","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:49:04Z","timestamp":1770187744000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Persistent neutrophil activation despite count normalization suggests immune dysregulation in exertional heat stroke"],"prefix":"10.3389","volume":"16","author":[{"given":"Yue","family":"Wang","sequence":"first","affiliation":[{"name":"Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences","place":["Hefei, Anhui, China"]},{"name":"University of Science and Technology of China","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siya","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency, Central Theater General Hospital of The People\u2019s Liberation Army of China","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Emergency, Central Theater General Hospital of The People\u2019s Liberation Army of China","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, The Affiliated Qingyuan Hospital (Qingyuan People\u2019s Hospital), Guangzhou Medical University","place":["Qingyuan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2015.09.014","article-title":"Cooling methods in heat stroke","volume":"50","author":"Gaudio","year":"2016","journal-title":"J Emerg Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra011089","article-title":"Heat stroke","volume":"346","author":"Bouchama","year":"2002","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2015.tb00612.x","article-title":"Heat stroke","volume":"5","author":"Leon","year":"2015","journal-title":"Compr Physiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.167.20.ioi70147","article-title":"Short- and long-term outcomes of heatstroke following the 2003 heat wave in Lyon, France","volume":"167","author":"Argaud","year":"2007","journal-title":"Arch Intern Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-200636110-00003","article-title":"Exercising in environmental extremes: a greater threat to immune function","volume":"36","author":"Walsh","year":"2006","journal-title":"Sports Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.abb.2018.01.004","article-title":"Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function","volume":"640","author":"Aratani","year":"2018","journal-title":"Arch Biochem Biophys"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nri1841","article-title":"Neutrophil serine proteases: specific regulators of inflammation","volume":"6","author":"Pham","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-12-077917","article-title":"The phagocytes: neutrophils and monocytes","volume":"112","author":"Dale","year":"2008","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1710-1492-2-3-98","article-title":"Mechanisms of degranulation in neutrophils","volume":"2","author":"Lacy","year":"2006","journal-title":"Allergy Asthma Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev.immunol.23.021704.115653","article-title":"How neutrophils kill microbes","volume":"23","author":"Segal","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00448","article-title":"Granule protein processing and regulated secretion in neutrophils","volume":"5","author":"Sheshachalam","year":"2014","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2018.06.006","article-title":"Neutrophils: Novel key players in Rheumatoid Arthritis. Current and future therapeutic targets","volume":"17","author":"Cecchi","year":"2018","journal-title":"Autoimmun Rev"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304918","article-title":"Adventitial CXCL1\/G-CSF expression in response to acute aortic dissection triggers local neutrophil recruitment and activation leading to aortic rupture","volume":"116","author":"Anzai","year":"2015","journal-title":"Circ Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2019.11.003","article-title":"Granulocyte colony stimulating factor (G-CSF) regulates neutrophils infiltration and periodontal tissue destruction in an experimental periodontitis","volume":"117","author":"Zhang","year":"2020","journal-title":"Mol Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.07.003","article-title":"Neutrophilic inflammation in asthma and association with disease severity","volume":"38","author":"Ray","year":"2017","journal-title":"Trends Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41649","article-title":"CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow","volume":"120","author":"Eash","year":"2010","journal-title":"J Clin Invest"},{"key":"B17","doi-asserted-by":"publisher","first-page":"12077","DOI":"10.1038\/ncomms12077","article-title":"Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins","volume":"7","author":"Tyrkalska","year":"2016","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2018","article-title":"The neutrophil\u2019s role during health and disease","volume":"99","author":"Liew","year":"2019","journal-title":"Physiol Rev"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3908061","DOI":"10.1155\/2017\/3908061","article-title":"The role of IL-17 and related cytokines in inflammatory autoimmune diseases","volume":"2017","author":"Kuwabara","year":"2017","journal-title":"Mediators Inflamm"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40779-019-0229-2","article-title":"Expert consensus on the diagnosis and treatment of heat stroke in China","volume":"7","author":"Liu","year":"2020","journal-title":"Mil Med Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/jes.0b013e3180a02bec","article-title":"Cold water immersion: the gold standard for exertional heatstroke treatment","volume":"35","author":"Casa","year":"2007","journal-title":"Exerc Sport Sci Rev"},{"key":"B22","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1097\/00000441-200402000-00002","article-title":"Correlation of neutrophil phagocytosis and lymphocyte adhesion molecules in exertional heat stroke","volume":"327","author":"Lu","year":"2004","journal-title":"Am J Med Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1209793","article-title":"Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia","volume":"88","author":"Pillay","year":"2010","journal-title":"J Leukoc Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.4A0816-354R","article-title":"Heat-shock protein-90 prolongs septic neutrophil survival by protecting c-Src kinase and caspase-8 from proteasomal degradation","volume":"103","author":"Gupta","year":"2018","journal-title":"J Leukoc Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1124\/jpet.103.063131","article-title":"Cloning and pharmacological characterization of CXCR1 and CXCR2 from Macaca fascicularis","volume":"310","author":"Hipkin","year":"2004","journal-title":"J Pharmacol Exp Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0408231","article-title":"The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice","volume":"84","author":"Bento","year":"2008","journal-title":"J Leukoc Biol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0226OC","article-title":"Attenuating heat-induced acute lung inflammation and injury by dextromethorphan in rats","volume":"46","author":"Yang","year":"2012","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.01087","article-title":"Role of the receptor for advanced glycation end products in heat stress-induced endothelial hyperpermeability in acute lung injury","volume":"11","author":"Zhou","year":"2020","journal-title":"Front Physiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-019-00983-6","article-title":"Regulatory T cells could improve intestinal barrier dysfunction in heatstroke","volume":"42","author":"Hu","year":"2019","journal-title":"Inflammation"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.2095-4352.2015.05.002","article-title":"Correlation of kidney injury and inflammatory response in rats with classic severe heatstroke","volume":"27","author":"Peng","year":"2015","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1136\/emj.2005.028290","article-title":"Risk factors for heat related death during the August 2003 heat wave in Paris, France, in patients evaluated at the emergency department of the Hopital Europeen Georges Pompidou","volume":"23","author":"Davido","year":"2006","journal-title":"Emerg Med J"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-129-3-199808010-00001","article-title":"Near-fatal heat stroke during the 1995 heat wave in Chicago","volume":"129","author":"Dematte","year":"1998","journal-title":"Ann Intern Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/SHK.0b013e3181818466","article-title":"The role of neutrophils in severe sepsis","author":"Alves-Filho","year":"2008","journal-title":"Shock"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-014-1721-3","article-title":"Plasma and lymphocyte Hsp72 responses to exercise in athletes with prior exertional heat illness","volume":"46","author":"Ruell","year":"2014","journal-title":"Amino Acids"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1113\/JP280518","article-title":"Exertional heat stroke leads to concurrent long-term epigenetic memory, immunosuppression and altered heat shock response in female mice","volume":"599","author":"Murray","year":"2021","journal-title":"J Physiol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1718617\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:31:34Z","timestamp":1771925494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1718617\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2025.1718617"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1718617","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"article-number":"1718617"}}