ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Persistent Neutrophil Activation Despite Count Normalization Suggests Immune Dysregulation in Exertional Heat Stroke
Provisionally accepted
- 1Department of Intensive Care Unit, Qingyuan People's Hospital, Qingyuan, China
- 2Department of Emergency, People's Liberation Army General Hospital of Central Theater Command, Wuhan, China
- 3Hefei BOE Hospital, Hefei, China
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Background: 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. Methods: 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. Results: At onset, EHS patients exhibited significant neutrophilia and elevated levels of IL-8, CXCL1, CXCL2, and IL-17 (all P < 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 < 0.0001). Furthermore, strong positive correlations were observed between the levels of CXCL1/CXCL2 and MPO/NE at disease onset. Conclusion: 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.
Keywords: Exertional heat stroke, Neutrophil Activation, Myeloperoxidase, Neutrophil Elastase, Cytokines, longitudinal study
Received: 04 Oct 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Liu, Xu, Tang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
ZHongzhi Tang
Yue Wang
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