Lipopolysaccharide-induced interleukin 8 production by human whole blood is enhanced by epinephrine and inhibited by hydrocortisone

Abstract

To determine the effect of epinephrine and hydrocortisone on lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) production, human whole blood was stimulated with LPS in the presence or absence of these stress hormones. Epinephrine caused a dose-dependent increase in LPS-induced IL-8 production, which was mediated exclusively via β-adrenergic receptors, as reflected by the facts that β (but not α) receptor blockade reversed the epinephrine effect and β (but not α) receptor stimulation reproduced the epinephrine effect. Further, elevating cellular cyclic AMP (cAMP) concentrations, a known effect of β-adrenergic stimulation, by addition of dibutyryl cAMP also enhanced LPS-induced IL-8 production. Epinephrine- induced upregulation of IL-10 production masked an even more pronounced stimulating effect of this hormone on IL-8 synthesis, as indicated by the finding that the extent of IL-8 upregulation was greater in the presence of anti-IL-10 than in the absence of anti-IL-10. Hydrocortisone dose- dependently inhibited LPS-induced IL-8 production and reversed epinephrine- induced enhancement of IL-8 production. Epinephrine and hydrocortisone have opposite effects on IL-8 production, which may be relevant for the understanding of endogenous and therapeutic stress hormone influences on IL- 8 mediated inflammation.