Temporal Coupling of Cortisol and Immune Cell Responses in Acute Psychosocial Stress

Acute psychosocial stress triggers coordinated neuroendocrine and immune responses, yet the temporal coupling between cortisol release and leukocyte redistribution in humans remains understudied. In a sample of 302 participants (aged 18 to 59 years; 64 % female) drawn from the Swedish Twin Registry, we characterized trajectories of neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) following the Trier Social Stress Test (TSST). Blood samples were collected at five timepoints (pre-stress, and at 5, 30, 60, and 90 minutes after stress), and plasma cortisol was measured at the first three timepoints. Linear mixed-effects models assessed the effects of time, cortisol response (area under the curve with respect to increase; AUC i ), and covariates (sex, age, body mass index; BMI) on leukocyte dynamics. The TSST induced canonical biphasic leukocyte responses: lymphocytes peaked 5 minutes post-stress and declined below baseline during recovery, while neutrophils showed sustained late-phase elevations. Higher cortisol responses were associated with stronger late lymphocyte suppression and higher NLR at 30 to 90 minutes after stress, but largely unrelated to neutrophil trajectories. Male participants exhibited greater cortisol reactivity and higher late NLR, older age was associated with blunted cortisol and neutrophil recovery, and higher BMI with attenuated early lymphocyte responses. These findings delineate a plausible phase-specific endocrine–immune coupling in humans where cortisol is linked to variation in lymphocyte redistribution and NLR fluctuations following acute stress. The results suggest a mechanism by which heightened or recurrent HPA-axis activation could influence post-stress inflammatory tone, plausibly contributing to vulnerability for stress-related psychiatric disorders.