title: Stress-induced modulation of NF-κB activation, inflammation-associated gene expression, and cytokine levels in blood of healthy men.
abstract: Acute psychosocial stress stimulates transient increases in circulating pro-inflammatory plasma cytokines, but little is known about stress effects on anti-inflammatory cytokines or underlying mechanisms. We investigated the stress kinetics and interrelations of pro- and anti-inflammatory measures on the transcriptional and protein level. Forty-five healthy men were randomly assigned to either a stress or control group. While the stress group underwent an acute psychosocial stress task, the second group participated in a non-stress control condition. We repeatedly measured before and up to 120min after stress DNA binding activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, whole-blood mRNA levels of NF-κB, its inhibitor IκBα, and of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6, and the anti-inflammatory cytokine IL-10. We also repeatedly measured plasma levels of IL-1ß, IL-6, and IL-10. Compared to non-stress, acute stress induced significant and rapid increases in NF-κB-BA and delayed increases in plasma IL-6 and mRNA of IL-1ß, IL-6, and IκBα (p's<.045). In the stress group, significant increases over time were also observed for NF-κB mRNA and plasma IL-1ß and IL-10 (p's<.055). NF-κB-BA correlated significantly with mRNA of IL-1β (r=.52, p=.002), NF-κB (r=.48, p=.004), and IκBα (r=.42, p=.013), and marginally with IL-6 mRNA (r=.31, p=.11). Plasma cytokines did not relate to NF-κB-BA or mRNA levels of the respective cytokines. Our data suggest that stress induces increases in NF-κB-BA that relate to subsequent mRNA expression of pro-inflammatory, but not anti-inflammatory cytokines, and of regulatory-cytoplasmic-proteins. The stress-induced increases in plasma cytokines do not seem to derive from de novo synthesis in circulating blood cells.
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kuebler
authors.affiliation: Biological and Health Psychology, University of Bern, Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Zuccarella-Hackl
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
authors.forename: Angela
authors.initials: A
authors.lastname: Arpagaus
authors.affiliation: Department of Psychology & Volen National Center for Complex Systems, Brandeis University, Waltham, MA, USA.
authors.forename: Jutta M
authors.initials: JM
authors.lastname: Wolf
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Farahmand
authors.affiliation: Department of Psychosomatic Medicine, Clinic Barmelweid, Barmelweid, Switzerland; Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: von Känel
authors.affiliation: Department of Clinical Psychology and Psychotherapy, University of Zurich, Zurich, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ehlert
authors.affiliation: Biological and Health Psychology, University of Bern, Bern, Switzerland; Biological Work and Health Psychology, University of Konstanz, Konstanz, Germany. Electronic address: petra.wirtz@uni-konstanz.de.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Wirtz
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood*; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D016328:NF-kappa B / Q000097:blood*; D013315:Stress, Psychological / Q000097:blood*
chemical_list: D016207:Cytokines; D016328:NF-kappa B
keywords: Cytokines; Interleukin-10; Interleukin-1β; Interleukin-6; IκBα; NF-κB; Stress; TSST; mRNA