NEUTROPHILS ACTIVATED BY GRANULOCYTE-COLONY-STIMULATING FACTOR SUPPRESS TUMOR-NECROSIS-FACTOR-ALPHA RELEASE FROM MONOCYTES STIMULATED BY ENDOTOXIN

We investigated the in vitro effects of granulocyte colony-stimulating factor (G-CSF) on tumor necrosis factor-alpha (TNF-alpha) release fro m monocytes. Peripheral blood monocytes and neutrophils were obtained from healthy donors (n = 8). Neutrophils alone, neutrophils plus monoc ytes, and monocytes alone were incubated with and without G-CSF (10 ng /ml) and were studied for TNF-alpha release; monocytes subsequently we re stimulated by endotoxin (lipopolysaccharide [LPS] at 10 and 1,000 n g/ml). Neutrophils alone did not produce TNF-alpha after LPS stimulati on irrespective of G-CSF treatment. TNF-alpha release from monocytes w as suppressed significantly by pretreatment with G-CSF in the presence of neutrophils (P < 0.01). Suppression of TNF-alpha release after LPS was not observed when monocytes were preincubated with G-CSF in the a bsence of neutrophils. TNF-alpha release from monocytes stimulated by LPS was not inhibited when monocytes were incubated with the supernata nt from G-CSF-activated neutrophils. Pretreatment with G-CSF inhibited intracellular TNF-alpha production, as measured by flow cytometry, of monocytes stimulated by LPS (P < 0.05). These data suggest that neutr ophils activated by G-CSF directly suppress TNF-alpha release from mon ocytes stimulated by LPS.