CYTOKINE REGULATION OF GM-CSF AND G-CSF SECRETION BY HUMAN UMBILICAL-CORD VEIN ENDOTHELIAL-CELLS (HUVEC)

The cytokine regulation of granulocyte-macrophage colony-stimulating f actor (GM-CSF) and G-CSF secretion by human umbilical cord vein endoth elial cells (HUVEC) using quantitative immunoassays was studied, Unsti mulated HUVEC produced no CSF. Interleukin 1 (IL-1), TNF and lipopolys accharides (LPS) had stimulatory effects, with IL-1 being the most pot ent, GM-CSF and G-CSF secretion followed the same pattern, except that more GM-CSF was secreted, Exposure to stimuli for 30 min induced secr etion, and detectable amounts in supernatants were found after 4 h inc ubation, CSF secretion was strictly regulated by the presence of a sti mulus in a concentration dependent manner, and there were no signs of any endogenous downregulatory mechanism, No other cytokine tested had any stimulatory effect of its own, However, addition of IL-3 to stimul ated HUVEC enhanced both GM-CSF and G-CSF secretion in a dose-dependen t manner, In addition, TNF, and to a lesser degree LPS, enhanced IL-1- induced secretion, The only cytokine with a prominent downregulatory e ffect was IFN-gamma, IL-4 and IL-10, which downregulate CSF secretion by monocytes, had only minor effects. (C) 1996 Academic Press Limited