Determinants of the NF-κB response to acute psychosocial stress in humans

The present study shows for the first time in human psychosocial stress the negative association of cortisol and NF-kappaB, a major inducer of inflammatory genes, parallels results from in vitro studies.

Abstract

Previous research has shown that psychosocial stress is associated with an increased activity of the transcription factor nuclear factor-kappaB (NF-kappaB), a major inducer of inflammatory genes. While considerable individual variation has been noted, factors contributing to this variation have not been described so far. Therefore, 29 healthy participants (35.8+/-12 yrs) were exposed to the Trier Social Stress Test. Blood was collected before and repeatedly afterward for determination of NF-kappaB activity, leukocyte subset numbers, cortisol, norepinephrine, and in vitro-stimulated IL-6 production. Additionally, age, sex, and ratings of perceived chronic and acute stress were assessed. Regression analyses revealed that older participants showed a lower NF-kappaB stress response compared to younger adults (beta= -.42, p=.026). Higher NF-kappaB stress responses were associated with lower cortisol stress responses (beta= -.37, p=.05), higher pre-stress IL-6 production (beta=.38, p=.043), and high chronic in combination with low acute stress, or vice versa (beta= -.61, p=.06). Norepinephrine and sex were not associated with NF-kappaB stress responses (all p.13). In summary, the present study shows for the first time in human psychosocial stress the negative association of cortisol and NF-kappaB. This parallels results from in vitro studies. Our finding of lower NF-kappaB stress responses in older age and in people with high chronic and acute stress might be interpreted as an adaptive dampening of NF-kappaB activity. In the absence of longitudinal data, however, this interpretation remains speculative.