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A Critical Rectal Temperature Defines Sex-Specific Leukocyte and Neutrophil Activation During Prolonged Passive Heat Exposure in Young Adults

Wei, B.; Xu, Y.; Wang, H.; Wang, F.

2025-10-13 immunology
10.1101/2025.10.11.681783 bioRxiv
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BackgroundProlonged heat exposure disrupts immune homeostasis and can precipitate acute systemic inflammation. However, the core temperature threshold that triggers sex-specific leukocyte and neutrophil activation during passive heat stress remains undefined. MethodsWe studied 52 males and 58 females exposed to wet-bulb temperatures of 32-35 {degrees}C. Rectal temperature (Trec) was continuously monitored, and blood samples were collected at 0.5 {degrees}C increments up to 38.6 {degrees}C. Leukocyte and neutrophil counts were modeled using quadratic and segmented regression to identify inflection points of immune activation. ResultsBoth leukocytes and neutrophils increased nonlinearly with rising Trec (p < 0.05). A critical Trec of 38.1 {degrees}C--closely aligns with the 38.0 {degrees}C occupational core temperature limits--marked an inflection in leukocyte responses: below this point, females showed steeper increases; whereas above it, males showed accelerated activation. Neutrophils demonstrated consistently greater mobilization in males across the entire temperature range (36.9-38.6 {degrees}C). ConclusionsA distinct core temperature threshold ([~]38.1 {degrees}C) governs immune cell activation and reveals sex-dependent response patterns. This finding provides an immunological rationale for current occupational het limits and highlights the importance of integrating sex-specific considerations into protective guidelines under extreme heat. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/681783v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@9620dorg.highwire.dtl.DTLVardef@47beborg.highwire.dtl.DTLVardef@6396daorg.highwire.dtl.DTLVardef@44c890_HPS_FORMAT_FIGEXP M_FIG C_FIG

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