Cell-free DNA, cytokine, and catecholamine levels did not differ between sexes under a matched body core temperature increase, despite females exhibiting a more rapid increase in rectal temperature.

PURPOSE: To compare cell-free DNA (cfDNA), catecholamine (CAT), and cytokine concentrations and the perceptual responses following rectal temperature-matched hot water immersion (HWI) in females and males.

METHODS

Twenty-two healthy young adults (9 females, 13 males) underwent HWI (water temperature 43-44 °C) until body rectal temperature (Tre) reached 39 °C. Blood samples to determine cfDNA, CAT, and cytokine concentrations were collected. Thermal perceptions, Tre, and heart rate (HR) were assessed throughout the intervention.

RESULTS

Females reached each Tre significantly faster than males (p < 0.001) and cooled more quickly during recovery (p = 0.023). HR and the physiological strain index increased similarly in both sexes. cfDNA increased twofold with rising Tre (main effect of time, p < 0.001) and no overall sex difference, although males showed higher values after 30 min of recovery (p = 0.046). Norepinephrine and epinephrine rose significantly during heating (p < 0.001), with no sex differences. Prolactin exhibited a stronger rise in females (sex × time interaction, p < 0.001), whereas tumor necrosis factor-α decreased only in males (p < 0.05). Interleukin-6 increased markedly in both sexes but was higher in males at baseline and early recovery (p < 0.05).

CONCLUSION

When exposed to matched Tre elevation, females and males showed similar cfDNA, CAT, and perceptual responses, despite females reaching target temperatures faster and cooling more rapidly. These findings highlight cfDNA as a temperature-dependent marker of thermal strain and support its use alongside classical neuroendocrine and immune markers to characterize heat-stress physiology.