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

Background: Prolonged 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. Methods: We studied 52 males and 58 females exposed to wet-bulb temperatures of 32–35 °C. Rectal temperature (Trec) was continuously monitored, and blood samples were collected at 0.5 °C increments up to 38.6 °C. Leukocyte and neutrophil counts were modeled using quadratic and segmented regression to identify inflection points of immune activation. Results: Both leukocytes and neutrophils increased nonlinearly with rising Trec (p < 0.05). A critical Trec of 38.1 °C–closely aligns with the 38.0 °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 °C). Conclusions: A distinct core temperature threshold (~38.1 °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.