Enhanced glucocorticoid sensitivity of cytokine release from circulating leukocytes stimulated with lipopolysaccharide in healthy male smokers.
Smoking is a strong cardiovascular risk factor that promotes inflammation. The source of elevated pro-inflammatory cytokines in the circulation of smokers is not fully understood. We investigated the release of pro-inflammatory cytokines from circulating leukocytes stimulated with lipopolysaccharide (LPS) and its inhibition by glucocorticoids in smokers and non-smokers. Ninety-three middle-aged apparently healthy men were categorized as smokers (> 10 cigarettes/day; n = 41) or life-long non-smokers (n = 52). Peripheral cortisol was assessed from overnight urine. C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha were measured in plasma. LPS-stimulated interleukin (IL)-6 and TNF-alpha release from harvested circulating leukocytes were assessed using an in vitro whole blood assay with and without co-incubation of increasing concentrations of either dexamethasone or hydrocortisone. Glucocorticoid sensitivity was defined as the concentration of glucocorticoids required that inhibits LPS-stimulated cytokine release by 50%. Smokers had higher CRP levels (p = .005) and a trend for higher basal TNF-alpha levels (p < .07), and they also showed lower IL-6 and TNF-alpha release after LPS-stimulation than non-smokers (p's < .001). While peripheral cortisol concentration showed no significant group difference, inhibition of LPS-stimulated leukocyte IL-6 and TNF-alpha release by either glucocorticoid was enhanced in smokers as compared to non-smokers (p's < .022). The finding suggests that, in spite of a low-grade systemic inflammation, smokers have decreased LPS-stimulated cytokine release from circulating leukocytes and greater glucocorticoid sensitivity of this cytokine release than non-smokers. Circulating leukocytes unlikely contribute to the elevated pro-inflammatory cytokine levels in the blood of smokers.
Department of Clinical Psychology II, University of Zurich, Zurich, Switzerland.
Petra H
PH
Wirtz
Roland
R
von Känel
Sabine
S
Kunz-Ebrecht
Ulrike
U
Ehlert
Joachim E
JE
Fischer
D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D012907:Smoking / Q000097:blood / Q000276:immunology* / Q000652:urine; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014556:Urine / Q000166:cytology
D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D002097:C-Reactive Protein; D006854:Hydrocortisone