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 proinflammat ory cytokine tumor necrosis factor, whereas hypercortisolemia 12 h to 7 days before the injection of LPS is associated with enhanced tumor n ecrosis factor release. To determine the effect of elevated cortisol l evels on the secretion of the antiinflammatory cytokine interleukin-10 (IL-10), 23 healthy men were given iv LPS (lot EC-5; 2 ng/kg) done or in combination with a continuous iv infusion of hydrocortisone (3 mu g/kg . min) for 6 h immediately before or 6, 12, or 144 h before LPS i njection. LPS induced a monophasic increase in plasma IL-10 concentrat ions that peaked after 2 h (162 +/- 27 pg/mL; P < 0.0001). In subjects who were infused with hydrocortisone directly before LPS administrati on, IL-10 concentrations were much higher (1784 +/- 331 pg/mL; P < 0.0 001 vs. LPS only), whereas hypercortisolemia 6, 12, or 144 h before LP S injection did not influence LPS-induced IL-10 levels. In human whole blood in vitro, hydrocortisone caused a dose-dependent reduction of L PS-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 p roperties of glucocorticoids.