Psychological stress activates interleukin-1beta gene expression in human mononuclear cells.
The pathophysiological mechanisms underlying the association between psychological stress and cardiovascular disease are unclear. Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are inflammatory cytokines playing a pivotal role in atherosclerosis. IL-1beta activates IL-6, and both cytokines are produced by peripheral blood mononuclear cells. One mechanism through which stress could promote atherosclerosis is by regulating mononuclear cell cytokine gene expression. We studied cardiovascular and cytokine responses in 32 healthy men participating in two 5-min mental tasks and in 10 controls. Blood pressure and heart rate, assessed using a Portapres-2, increased significantly following tasks in all participants. Plasma IL-6 levels, determined by ELISA, also increased following tasks, with maximum levels detected 2h post-stress. Quantitative RT-PCR analysis showed that mononuclear cell IL-1beta gene expression rose significantly at 30 min post-stress and remained elevated at 75 and 120 min. Increases in IL-1beta gene expression correlated positively with plasma IL-6 responses, cardiovascular responses, subjective stress ratings, and anxiety symptoms. No changes were detected in controls. Stress-induced activation of mononuclear IL-1beta is a novel mechanism potentially linking stress and heart disease. This mechanism could also play a role in other inflammatory diseases exacerbated by stress.
Brydon
Lena
L
The Psychobiology Group, Department of Epidemiology and Public Health, University College London, London, UK. l.brydon@public-health.ucl.ac.uk
Edwards
Susan
S
Jia
Haiyan
H
Mohamed-Ali
Vidya
V
Zachary
Ian
I
Martin
John F
JF
Steptoe
Andrew
A
D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D005786:Gene Expression Regulation; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012016:Reference Values; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6