title: Response and habituation of pro- and anti-inflammatory gene expression to repeated acute stress.
abstract: BACKGROUND
  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 120min 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.
authors: Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States.
authors: Christine M
authors: CM
authors: McInnis
authors: Davis School of Gerontology, University of Southern California, Los Angeles, CA, United States.
authors: Diana
authors: D
authors: Wang
authors: Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States.
authors: Danielle
authors: D
authors: Gianferante
authors: Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States.
authors: Luke
authors: L
authors: Hanlin
authors: Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States.
authors: Xuejie
authors: X
authors: Chen
authors: Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States.
authors: Myriam V
authors: MV
authors: Thoma
authors: Department of Psychology and Volen National Center for Complex Systems, Brandeis University, Waltham, MA, United States. Electronic address: rohleder@brandeis.edu.
authors: Nicolas
authors: N
authors: Rohleder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics* / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism; D012463:Saliva / Q000737:chemistry; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D020672:I-kappa B Proteins; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D006854:Hydrocortisone
keywords: Gene expression; Habituation; IL-6, IL-1β, NF-κB, IκB; Inflammation; Stress