Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin 6 production in human whole blood.
Sepsis and lipopolysaccharide (LPS) trigger the systemic release of both cytokines and catecholamines. Cytokines are known to be capable of eliciting a stress hormone response in vivo. The present study sought insight into the effect of noradrenaline on LPS-induced release of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6) in human whole blood. Whole blood was incubated with LPS for 4 h at 37 degrees C in the presence and absence of noradrenaline and/or specific alpha and beta antagonists and agonists. Noradrenaline caused a dose-dependent inhibition of LPS-induced TNF and IL-6 production. This effect could be completely prevented by addition of the specific beta 1, antagonist metoprolol, while it was not affected by the alpha antagonist phentolamine. Specific beta-adrenergic stimulation by isoprenaline mimicked the inhibiting effect of noradrenaline on LPS-evoked cytokine production, whereas alpha-adrenergic stimulation by phenylephrine had no effect. Fluorescence-activated cell sorter analysis demonstrated that beta-adrenergic stimulation had no effect on LPS binding to and internalization into mononuclear cells or on the expression of CD14, the major receptor for LPS on mononuclear cells. In acute sepsis, enhanced release of noradrenaline may be part of a negative feedback mechanism meant to inhibit ongoing TNF and IL-6 production.
van der Poll
T
T
Center of Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, University of Amsterdam, The Netherlands.
Jansen
J
J
Endert
E
E
Sauerwein
H P
HP
van Deventer
S J
SJ
D000328:Adult; D000242:Cyclic AMP / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D013566:Sympathomimetics; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D008790:Metoprolol; D009638:Norepinephrine; D010646:Phentolamine