Epinephrine attenuates down-regulation of monocyte tumor necrosis factor receptors during human endotoxemia.
Epinephrine inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production by increasing intracellular cAMP concentrations. Because agents that increase cAMP levels can enhance TNF receptor expression in vitro, granulocyte and monocyte TNF receptors were determined by FACS-analysis in 7 normal humans who were receiving a constant 24-h infusion of epinephrine (30 ng/kg/min), and in 15 normal subjects after intravenous injection of LPS (2 ng/kg), while they were receiving a continuous infusion of epinephrine started either 3 h (EPI-3) or 24 h (EPI-24) before LPS injection or an infusion of normal saline (LPS; n = 5 per group). Infusion of epinephrine per se did not influence TNF receptor expression. LPS induced a transient decrease in monocyte TNF receptors and a more sustained decrease in granulocyte TNF receptors (both P < 0.05). EPI-3 partly prevented LPS-induced down-modulation of monocyte TNF receptors (P < 0.05 vs. LPS only), but did not affect LPS-induced down-modulation of granulocyte TNF receptors. EPI-24 had no effect on TNF receptor expression. These data suggest that epinephrine not only influences the bioavailability of TNF by an effect on the production of this proinflammatory cytokine, but also by modulating the expression of its receptors.
van der Poll
T
T
Department of Surgery, Cornell University Medical College, New York, USA.
Calvano
S E
SE
Kumar
A
A
Coyle
S M
SM
Lowry
S F
SF
D000328:Adult; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology*; D019446:Endotoxemia / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000187:drug effects*
D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D004837:Epinephrine