Reduced glucocorticoid sensitivity of monocyte interleukin-6 release in male employees with high plasma levels of tumor necrosis factor-α

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2004
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von Känel, Roland
Kunz-Ebrecht, Sabine
Ehlert, Ulrike
Fischer, Joachim E.
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Cytokine production by monocytes plays a key role in atherosclerosis. In vitro, preincubation of whole blood with tumor necrosis factor (TNF)-alpha regulates interleukin (IL)-6 release from monocytes stimulated with lipopolysaccharide (LPS). We investigated whether plasma levels of TNF-alpha would also relate to LPS-stimulated monocyte IL-6 production and the inhibitory effect of a glucocorticoid on this process. 224 middle-aged men were assigned to three groups according to tertiles of plasma levels of TNF-alpha. Subjects in the highest tertile (high TNF-alpha, n = 75) were compared to those in the lowest (low TNF-alpha, n = 74) and medium tertile (medium TNF-alpha, n = 75), respectively. In vitro monocyte IL-6 release following lipopolysaccharide (LPS)-stimulation was assessed with and without coincubation with incremental doses of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting IL-6 release by 50%. Subjects with high TNF-alpha showed more IL-6 release after LPS-stimulation than those with low TNF-alpha (p =.011). Monocyte glucocorticoid sensitivity was lower in subjects with high levels of TNF-alpha than in subjects with low (p =.014) and with medium (p =.044) levels of TNF-alpha. Results held significance when a set of classic cardiovascular risk factors was controlled for. Our findings suggest that elevated plasma levels of TNF-alpha might enhance LPS-stimulated IL-6 release from circulating monocytes. Such a mechanism might contribute to exaggerated monocyte cytokine release in vivo to any LPS-like danger signal such as related to an infection or cellular stress thereby promoting atherosclerosis.

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Fachgebiet (DDC)
150 Psychologie
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Cardiovascular disease; Cytokines; Inflammation; Monocytes; Glucocorticoid sensitivity
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ISO 690WIRTZ, Petra H., Roland VON KÄNEL, Sabine KUNZ-EBRECHT, Ulrike EHLERT, Joachim E. FISCHER, 2004. Reduced glucocorticoid sensitivity of monocyte interleukin-6 release in male employees with high plasma levels of tumor necrosis factor-α. In: Life sciences. 2004, 75(1), pp. 1-10. ISSN 0024-3205. eISSN 1879-0631. Available under: doi: 10.1016/j.lfs.2003.11.024
BibTex
@article{Wirtz2004Reduc-30679,
  year={2004},
  doi={10.1016/j.lfs.2003.11.024},
  title={Reduced glucocorticoid sensitivity of monocyte interleukin-6 release in male employees with high plasma levels of tumor necrosis factor-α},
  number={1},
  volume={75},
  issn={0024-3205},
  journal={Life sciences},
  pages={1--10},
  author={Wirtz, Petra H. and von Känel, Roland and Kunz-Ebrecht, Sabine and Ehlert, Ulrike and Fischer, Joachim E.}
}
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