Glucocorticoids can down-regulate immune activity, but acute stress has been reported to increase both cortisol and levels of plasma cytokines. We investigated individual differences in cortisol responses and their associations with proinflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), cardiovascular activity, and mental health. Saliva samples and blood were taken from 199 healthy middle-aged participants of the Whitehall II cohort at baseline, immediately after stress and 45min later. We defined the 40% of participants with the highest cortisol response to stress as the cortisol responder group and 40% with the lowest response as the cortisol non-responder group. Plasma IL-6 was higher and the IL-1ra response to stress was greater in the cortisol non-responder group. The cortisol non-responders showed lower heart rate variability than the cortisol responders. The cortisol responder group experienced more subjective stress during the tasks and reported more impaired mental health than the non-responders. We conclude that individual variations in neuroendocrine stress responsivity may have an impact on proinflammatory cytokines, and that both high and low cortisol stress responsiveness has potentially adverse effects.

To understand the underlying genetic and environmental sources of individual variation in basal cortisol levels, we collected salivary cortisol at awakening and at six fixed time points during the day in adult twins and their singleton siblings. Reported time of awakening was verified with heart rate and body movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins and 229 singleton siblings from 309 twin families. No differences in cortisol means and variances were found between twins and singleton siblings. Additionally, the correlations for DZ twins and siblings were not significantly different, indicating generalizability of twin study results to the general population. Genetic model fitting showed heritability for cortisol levels during the awakening period (34% for cortisol level at awakening and 32% for cortisol level at 30min after awakening) but not for cortisol levels later during the day. The current study shows that, while cortisol levels in the awakening period are influenced by genetic factors, cortisol levels throughout most of the day are not heritable, indicating that future gene finding studies for basal cortisol should focus on the first hour post-awakening.