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).
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%.
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.
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.
From Department of Behavioral Sciences, Swiss Federal Institute of Technology (P.H.W., R.v.K., P.S., K.F., J.E.F.), Zurich; Department of Clinical Psychology II, University of Zurich (U. E.), Zurich, Switzerland
Address reprint requests to: Joachim E. Fischer, MD, MSc, Department of Behavioral Sciences, Swiss Federal Institute of Technology, Turnerstrasse 1, CH-8092 Zurich, Switzerland. Email: firstname.lastname@example.org
Received for publication April 26, 2002; revision received September 30, 2002
This study was supported by grants from EADS (Werk Augsburg, Germany), and from the Swiss Federal Institute of Technology.