HPA-axis and inflammatory reactivity to acute stress is related with basal HPA-axis activity

Psychoneuroendocrinology. 2017 Apr;78:168-176. doi: 10.1016/j.psyneuen.2017.01.035. Epub 2017 Feb 6.


Introduction: Inflammation is drawing attention as pathway between psychosocial stress and health, and basal HPA axis activity has been suggested to exert a consistent regulatory influence on peripheral inflammation. Here we studied the relationship between basal HPA axis activity and inflammatory and HPA axis acute stress reactivity.

Methods: We recruited 48 healthy individuals and collected saliva for diurnal cortisol sampling at 6 points. Participants were previously exposed to the Trier Social Stress Test (TSST) on two consecutive days. Plasma interleukin-6 (IL-6) and salivary cortisol reactivity to acute stress were measured, and their relationships with basal HPA axis activity were analyzed.

Results: Steeper cortisol awakening response (CAR) linear increase was related with stronger cortisol stress reactivity (γ=0.015; p=0.042) and marginally significantly with greater habituation (γ=0.01; p=0.066). Greater curvilinearity of CAR was related with stronger cortisol reactivity (γ=-0.014; p=0.021) and greater cortisol habituation (γ=-0.011; p=0.006). Steeper daily linear decline was related with significant or marginally significantly stronger cortisol and IL-6 reactivity (cortisol: γ=-0.0004; p=0.06; IL-6: γ=-0.028; p=0.031) and greater habituation (cortisol: γ=-0.002; p=0.009, IL-6: γ=-0.015; p=0.033). Greater curvilinearity of daily decline was related with stronger IL-6 reactivity (γ=0.002; p=0.024) and also greater cortisol and IL-6 habituation (cortisol: γ=0.00009; p=0.03, IL-6: γ=0.001; p=0.024).

Conclusions: Patterns of basal HPA axis activity that are related with healthier outcomes were found to be related with stronger initial cortisol and IL-6 reactivity and greater habituation. This is an important step in understanding the long-term health implications of acute stress responsiveness, and future studies should employ longitudinal designs to identify the direction of these relationships.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Female
  • Humans
  • Hydrocortisone / analysis*
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Inflammation / blood
  • Inflammation / physiopathology*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology*
  • Saliva / chemistry
  • Stress, Psychological / blood
  • Stress, Psychological / physiopathology*
  • Wakefulness / physiology
  • Young Adult


  • Biomarkers
  • Interleukin-6
  • Hydrocortisone