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Wirtz, P H; von Känel, R; Kunz-Ebrecht, S; Ehlert, U; Fischer, J E (2004). Reduced glucocorticoid sensitivity of monocyte interleukin-6 release in male employees with high plasma levels of tumor necrosis factor-alpha. Life Sciences, 75(1):1-10.

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Abstract

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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4 citations in Web of Science®
5 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:06 Faculty of Arts > Institute of Psychology
DDC:150 Psychology
Date:2004
Deposited On:31 Aug 2010 07:51
Last Modified:27 Nov 2013 18:22
Publisher:Elsevier
ISSN:0024-3205
Publisher DOI:10.1016/j.lfs.2003.11.024
PubMed ID:15102517

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