Reduced glucocorticoid sensitivity of monocyte interleukin-6 production in male industrial employees who are vitally exhausted
METADATA ONLY
Loading...
Author / Producer
Date
2003-07
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
METADATA ONLY
Data
Rights / License
Abstract
Objective:
Proinflammatory changes are thought to link vital exhaustion with adverse cardiovascular outcomes. Monocytes play a central role in the pathogenesis of atherosclerotic lesions and are a major source of circulating cytokines. We hypothesized that vital exhaustion may alter the regulation of monocyte activity, as measured by lipopolysaccharide (LPS)-stimulated and glucocorticoid inhibited release of the proinflammatory cytokine interleukin-6 (IL-6).
Methods:
In 166 middle-aged apparently healthy men, vital exhaustion was measured by the Shortened Maastricht Exhaustion Questionnaire. Subjects in the highest quartile (highly exhausted, N = 38) were compared with those in the second and third quartiles (moderately exhausted N = 89) vs. those in the lowest quartile (nonexhausted, N = 39) in terms of plasma C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) levels, and as to IL-6 release after LPS stimulation in vitro. Inhibition of IL-6 release was determined by coincubation with increasing concentrations of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting IL-6 release by 50%.
Results:
Highly exhausted individuals had higher CRP levels than nonexhausted subjects (p = .008). LPS-stimulated IL-6 release was not significantly different between groups. However, in highly exhausted participants, dexamethasone was less able to inhibit IL-6 release (p = .010), and the glucocorticoid sensitivity was lower (p = .003) than in nonexhausted subjects.
Conclusions:
In highly exhausted individuals, glucocorticoids exert less suppressive action on monocyte IL-6 release than in nonexhausted subjects. This finding points to altered regulation of monocyte cytokine production as one possible pathway linking exhaustion with atherosclerosis.
Permanent link
Publication status
published
Editor
Book title
Journal / series
Volume
65 (4)
Pages / Article No.
672 - 678
Publisher
Lippincott Williams & Wilkins
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Vital exhaustion; Coronary artery disease; Glucocorticoid sensitivity; Monocytes; Cytokines; Interleukin-6