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

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.