Hypercortisolemia increases plasma interleukin-10 concentrations during human endotoxemia : A clinical research center study

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 relea...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 1996-10, Vol.81 (10), p.3604-3606
Main Authors: VAN DER POLL, T, BARBER, A. E, COYLE, S. M, LOWRY, S. F
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Dose-Response Relationship, Drug
Endotoxemia - blood
Epinephrine - administration & dosage
Epinephrine - pharmacology
Escherichia coli
Female
General aspects
Human infectious diseases. Experimental studies and models
Humans
Hydrocortisone - administration & dosage
Hydrocortisone - blood
Hydrocortisone - pharmacology
Infectious diseases
Interleukin-10 - blood
Lipopolysaccharides
Male
Medical sciences
Tumor Necrosis Factor-alpha - metabolism
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Summary: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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.81.10.3604