title: Hypercortisolemia increases plasma interleukin-10 concentrations during human endotoxemia--a clinical research center study.
abstract: Hypercortisolemia directly before the administration of endotoxin (LPS) to normal humans completely prevents the release of the proinflammatory cytokine tumor necrosis factor, whereas hypercortisolemia 12 h to 7 days before the injection of LPS is associated with enhanced tumor necrosis factor release. To determine the effect of elevated cortisol levels on the secretion of the antiinflammatory cytokine interleukin-10 (IL-10), 23 healthy men were given iv LPS (lot EC-5; 2 ng/kg) alone or in combination with a continuous iv infusion of hydrocortisone (3 micrograms/kg.min) for 6 h immediately before or 6, 12, or 144 h before LPS injection. LPS induced a monophasic increase in plasma IL-10 concentrations that peaked after 2 h (162 +/- 27 pg/mL; P < 0.0001). In subjects who were infused with hydrocortisone directly before LPS administration, IL-10 concentrations were much higher (1784 +/- 331 pg/mL; P < 0.0001 vs. LPS only), whereas hypercortisolemia 6, 12, or 144 h before LPS injection did not influence LPS-induced IL-10 levels. In human whole blood in vitro, hydrocortisone caused a dose-dependent reduction of LPS-induced IL-10 levels. Further, hydrocortisone reversed the increase in IL-10 concentrations by epinephrine in LPS-stimulated whole blood. Stimulation of IL-10 release may contribute to the antiinflammatory properties of glucocorticoids.
authors.affiliation: Cornell University Medical College, Department of Surgery, New York, New York 10021, USA.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: A E
authors.initials: AE
authors.lastname: Barber
authors.forename: S M
authors.initials: SM
authors.lastname: Coyle
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000097:blood*; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology; D004926:Escherichia coli; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D016753:Interleukin-10 / Q000097:blood*; D008070:Lipopolysaccharides; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D006854:Hydrocortisone; D004837:Epinephrine