title: Reduced glucocorticoid sensitivity of monocyte interleukin-6 production in male industrial employees who are vitally exhausted.
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-alpha (TNF-alpha) 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.
authors.affiliation: Department of Behavioral Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Wirtz
authors.forename: Roland
authors.initials: R
authors.lastname: von Känel
authors.forename: Pia
authors.initials: P
authors.lastname: Schnorpfeil
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ehlert
authors.forename: Karl
authors.initials: K
authors.lastname: Frey
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Fischer
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000209:etiology*; D002097:C-Reactive Protein / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D004651:Employment; D005221:Fatigue / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007221:Industry; D007249:Inflammation / Q000097:blood / Q000209:etiology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012720:Severity of Illness Index; D013557:Switzerland; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D002097:C-Reactive Protein