123. Response and habituation of pro- and anti-inflammatory gene expression to repeated psychosocial stress

Abstract

Rationale: Acute stress is accompanied by an inflammatory response and some individuals show sensitization to repeated stress. Increased peripheral inflammation is a risk factor for many 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: We recruited n = 31 healthy individuals and examined gene expression of IL-6, IL-1beta, RelA and IkappaB before, 30 and 120 min after exposure to the Trier Social Stress Test (TSST) on two days. We assessed the inflammatory response by measuring plasma IL-6, and cortisol as the major anti-inflammatory stress hormone. Results: Stress exposure induced inflammatory and cortisol responses (IL-6: F = 49.3, p F = 13.7, p ∗ time interaction F = 4.2, p = 0.011) but IL-6 responses did not (n.s.). IL-6 and IL-1beta gene expression increased on Day 1, but not on Day 2 (day ∗ time interaction: IL-6: F = 106, p = 0.001; IL-1beta: F = 7.9, p = 0.006). RelA expression increased on both days (time effect F = 5.0, p = 0.013). IkB expression increased then decreased below baseline on Day 1, and decreased post-TSST on Day 2 (day ∗ time interaction: F (2,54) = 5.4, p = 0.08). There was no relationship between IL-1Beta, IkB, and RelA with plasma IL-6 or cortisol, or between cortisol and plasma IL-6. Conclusions: Taken together, results show a response pattern of pro- and anti-inflammatory gene expression characterized by differential stress responses and habituation patterns that are in disjunction with patterns of cortisol and plasma IL-6 responses to repeated stress. This indicates that increases in plasma concentrations of inflammatory cytokines are unlikely to originate solely from de novo transcription within PBMCs, but that alternative or additional sources of plasma inflammatory cytokines need to be explored.