IN-VITRO BIOSYNTHESIS OF LEUKEMIA INHIBITORY FACTOR HUMAN INTERLEUKINFOR DA CELLS BY HUMAN ENDOTHELIAL-CELLS - DIFFERENTIAL REGULATION BY INTERLEUKIN-1-ALPHA AND GLUCOCORTICOIDS

Endothelial cells (EC) may represent a major source of cytokines in th e bone marrow, In this study we have examined the production and the r egulation of the production of leukemia inhibitory factor/human interl eukin for DA cells (LIF/HILDA) by EC. Human umbilical vein endothelial cells (HU-VEC) were chosen as a working model as they are a well know n source of cytokines, These cells secrete LIF/HILDA (90 pg/mL/10(6) c ells/48 h) in basal conditions, This secretion is profoundly altered b y interleukin-1 alpha (IL-1 alpha). Secretion of LIF/HILDA is increase d threefold on stimulation with IL-1 alpha at a concentration of 100 I U/mL, The secreted protein is bioactive as demonstrated by its prolife rative effects on DA1a cells. Modulation of the production of LIF/HILD A by glucocorticoids (GC) was also examined. In striking contrast to w hat was observed for IL-1 alpha, the synthetic GC dexamethasone (DXM) at a concentration of 10(-6) mol/L consistently inhibited the basal se cretion of LIF/HILDA by an average of threefold and suppressed the IL- 1 alpha-induced increase of the secretion of this cytokine by HUVEC. i n an effort to extend results obtained with HUVEC to the bone marrow e ndothelium, we have also examined the production of LIF/HILDA by human bone marrow endothelial cells (HBMEC). Our study shows that HBMEC are quantitatively a very important source of this cytokine (above 7.25 n g/mL/10(6) cells/48 h) suggesting that they are a major source of LIF/ HILDA in the bone marrow. Again, IL-1 alpha proved to be a very potent stimulus for the secretion of LIF/HILDA and synthetic GC such as DXM when used at a concentration of 10(-6) mol/L inhibited by an average o f threefold the basal secretion of LIF/HILDA and had a suppressive eff ect on the IL-1 alpha-induced increase of this secretion, The downregu lation of LIF/HILDA production in the bone marrow by GC may be importa nt to understand the effects of GC on hematopoiesis. (C) 1995 by The A merican Society of Hematology.