Response and habituation of pro- and anti-inflammatory gene expression to repeated acute stress

Abstract

Introduction Acute stress induces increases in plasma inflammatory mediators, which do not habituate to repeated stress. Inflammation is a risk factor for age-related illnesses, highlighting the need to understand factors controlling inflammation. No studies have examined changes in pro- and anti-inflammatory gene expression in response to repeated acute stress in humans. Methods RNA was isolated from peripheral blood before, 30 and 120 minutes after exposure of n=32 healthy human participants to the Trier Social Stress Test (TSST) on two days. Gene expression of interleukin (IL)-6, IL-1β, nuclear factor (NF)-κB and IκB was measured repeatedly on both days. We further assessed leukocyte numbers, plasma IL-6, and salivary cortisol. Results Stress induced IL-6 (F=44.7; p<0.001) and cortisol responses (F=18.6; p<0.001). Cortisol responses habituated (F=5.1, p=0.003), but IL-6 responses did not (n.s.). All genes increased in response to initial stress (IL-6: F=3.8; p=0.029; IL-1β: F=7.1; p=0.008; NF-κB: F=5.1; p=0.009; IκB; F=4.7; p=0.013) and showed habituation to repeated stress (IL-6: t=2.3; p=0.03; IL-1β: t=3.9; p=0.001; NF-κB: t=2.1; p=0.041; IκB: t=3.1; p=0.005). Day 1 responses of IL-1β and IκB were not explained by changes in leukocyte populations, but IL-6 and NF-κB, as well as most day 2 changes were not independent of leukocyte populations. Conclusions Stress response and habituation of pro- and anti-inflammatory gene expression as found here might indicate that even on an intracellular level, inflammatory responses to acute stress are adaptive in that they respond to initial, but habituate to repeated, similar stress. Future studies will need to test whether non-habituation is predictive of disease.

Repeating patterns of sleep restriction and recovery: Do we get used to it?

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The effects of acute psychological stress on circulating and stimulated inflammatory markers: A systematic review and meta-analysis

“…Individuals vary markedly in the magnitude of change in inflammatory mediators in response to acute stress and there is some evidence that this variability is relatively stable across time (Von Kanel 2006; Breines et al, 2014; Lockwood, John-Henderson, Marsland, 2016), and may even increase in magnitude in response to repeat testing (Rohleder, 2014; McInnis et al, 2015). Thus, it is conceivable that there is a meaningful distribution of differences in stress reactivity that may form a physiological basis for differences in susceptibility to disease.…”

Stress-induced release of matrix metalloproteinase-9 in patients with coronary artery disease: The possible influence of cortisol

“…Twenty min after stress, as many as two-thirds of the study participants exhibited cortisol levels that were lower than pre-test levels. According to previous studies, a peak response in cortisol is expected to occur 15-25 min after a laboratory mental stressor followed by a rapid decline reaching below pre-test levels (Kunz-Ebrecht et al 2003, Brydon 2010, McInnis et al 2015. However, in one study of healthy volunteers, cortisol levels were shown to be lower already 20 min after stress compared with pre-test levels (Steptoe et al 2001).…”