EPINEPHRINE ATTENUATES DOWN-REGULATION OF MONOCYTE TUMOR-NECROSIS-FACTOR RECEPTORS DURING HUMAN ENDOTOXEMIA

Epinephrine inhibits lipopolysaccharide (LPS)-induced tumor necrosis f actor (TNF) production by increasing intracellular cAMP concentrations . Because agents that increase cAMP levels can enhance TNF receptor ex pression in vitro, granulocyte and monocyte TNF receptors were determi ned by FACS analysis in normal humans who, were receiving a constant 2 4-h infusion of epinephrine (30 ng/kg/min), and in 15 normal subjects after intravenous injection of LPS (2 ng/kg), while they were receivin g a continuous infusion of epinephrine started either 3 h (EPI-3) or 2 4 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 T NF receptor expression. LPS induced a transient decrease in monocyte T NF receptors and a more sustained decrease in granulocyte TNF receptor s (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 n o effect on TNF receptor expression. These data suggest that epinephri ne not only influences the bioavailability of TNF by an effect on the production of this proinflammatory cytokine, but also by modulating th e expression of its receptors.