ENDOTOXIN INDUCES DOWN-REGULATION OF TUMOR-NECROSIS-FACTOR RECEPTORS ON CIRCULATING MONOCYTES AND GRANULOCYTES IN HUMANS

Leukocytes rapidly lose their surface receptors for tumor necrosis fac tor (TNF) after exposure to various stimuli in vitro. To assess the ef fect of endotoxin on cellular TNF receptors in humans in vivo, binding of biotinylated TNF to circulating monocytes and granulocytes was det ermined by fluorescence-activated cell sorter analysis in six healthy subjects after intravenous injection of endotoxin (lot EC-5, 20 U/kg). Endotoxin administration was associated with a transient decrease in monocyte TNF receptors, reaching a nadir after 2 hours (P < .0001), an d a more sustained decrease in granulocyte TNF receptors (P < .001). A lthough the decrease in cellular TNF receptors coincided with increase s in soluble TNF receptors types I and II, no correlations were observ ed between trough monocyte or granulocyte TNF receptors and peak plasm a concentrations of soluble TNF receptors. Stimulation of human whole blood with endotoxin resulted in reduced expression of both type I and type II TNF receptors on monocytes and granulocytes. Endotoxin induce s downmodulation of monocyte and granulocyte TNF surface receptors in humans in vivo, which may represent a mechanism to reduce excessive ac tivity of TNF during systemic infection. (C) 1995 by The American Soci ety of Hematology.