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: T van der Poll, A E Barber, S M Coyle, S F Lowry
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 81 Issue 10 Pg. 3604-6 (Oct 1996) ISSN: 0021-972X [Print] United States
• PMID: 8855809 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Hydrocortisone
• Epinephrine

Topics

• Adult
• Dose-Response Relationship, Drug
• Endotoxemia (blood)
• Epinephrine (administration & dosage, pharmacology)
• Escherichia coli
• Female
• Humans
• Hydrocortisone (administration & dosage, blood, pharmacology)
• Interleukin-10 (blood)
• Lipopolysaccharides
• Male
• Tumor Necrosis Factor-alpha (metabolism)