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Updated: May 9, 2026

A Preclinical Model of Exertional Heat Stroke in Mice
Published on: July 1, 2021
Core temperature-dependent leukocyte and neutrophil responses during prolonged heat exposure
Yi Xu1, Haojian Wang1, Fèlix Faming Wang1
1Centre for Molecular Biosciences and Non-Communicable Diseases Research, College of Safety Science and Engineering, Xi'an University of Science and Technology, Xi'an, China.
Background:
Prolonged indoor heat exposure disrupts immune homeostasis and can precipitate acute systemic inflammation. However, the core temperature threshold triggering sex-specific immune cell (leukocytes and neutrophils) mobilization during passive indoor heat stress remains undefined.
Methods:
We studied 68 males and 46 females exposed to wet-bulb temperatures (T w) of 32-35 °C. Rectal temperature (T rec) was continuously monitored, and blood samples were collected at 0.5 °C increments up to 38.9 °C. Leukocyte and neutrophil counts were modeled using quadratic and segmented mixed-effects models to identify inflection points of immune activation.
Results:
Both leukocytes and neutrophils increased nonlinearly with rising T rec (p < 0.05). Estimated T rec breakpoints occurred at approximately 38 °C, with overlapping 95% confidence intervals across sexes and cell types, indicating a transition to more rapid immune cell mobilization. This breakpoint was comparable to commonly cited thresholds for limiting excessive heat strain. Below the breakpoint, females exhibited steeper increases in both leukocytes and neutrophils, whereas above it, males showed greater acceleration, particularly for leukocytes. Neutrophil responses were consistently greater in males across the full temperature range (36.4-38.9 °C).
Conclusions:
A distinct core temperature threshold (~ 38.0 °C) governs accelerated immune cell mobilization and reveals sex-dependent response patterns. These findings provide an immunological rationale for current occupational heat limits and emphasize the importance of integrating sex-specific considerations into protective guidelines under extreme heat conditions.
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