Persistent neutrophil activation despite count normalization suggests immune dysregulation in exertional heat stroke

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.