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

Abstract

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.

Figure 1

(A) and (B) show HPA axis and inflammatory responses to repeated stress. Both HPA axis (A) and the inflammatory system (B) were activated to acute stress. During repeated exposure, HPA axis showed habituation while IL-6 showed sensitization. (C) shows the diurnal curve of HPA axis, with a rapid increase in the first hour upon awakening and a slow decline throughout rest of the day.

Figure 2

Factors that were related with CAR. (A) Young participants generally had higher levels of cortisol than older participants, and females had steeper linear increase of CAR. (B) Participants with higher cortisol responses to initial stress had a steeper linear increase and greater curvilinearity. (C) Participants with stronger cortisol habituation had a steeper linear increase, and greater curvilinearity (Q1= 1^st quartile, Q3= 3^rd quartile).

Figure 3

(A) Participants with higher cortisol responses to initial stress had steeper linear decreases of diurnal cortisol. (B) Participants with stronger cortisol habituation had steeper linear decreases and greater curvilinearity of diurnal cortisol (Q1= 1st quartile, Q3= 3rd quartile).

Figure 4

(A) Participants with higher IL-6 response during first stress exposure had steeper daily cortisol decrease and greater curvilinearity. (B) Participants with stronger IL-6 habituation had steeper daily cortisol decrease and greater curvilinearity (Q1= 1st quartile, Q3= 3rd quartile).