GRANULOCYTE COLONY-STIMULATING FACTOR DOES NOT ENHANCE ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN GUINEA-PIGS

We studied recombinant human granulocyte colony-stimulating factor (G-CSF) in terms of its hematopoietic and neutrophil-activating effects on acute lung injury induced by endotoxin. Guinea pigs were divided into four groups: (1) saline control animals, (2) endotoxin alone, (3) cyclophosphamide (CPA) + endotoxin, and (4) G-CSF + endotoxin. A G-CSF dose of 20-mu-g/kg was given subcutaneously twice a day for 5 days. Animals were observed for 4 h after intravenously administered endotoxin (0.02 and 2.0 mg/kg) with serial measurements of complete blood counts and hemodynamics. Lung extravascular water, [I-125]albumin leakage in lung tissue, and histopathologic features were examined st death. The endotoxin-alone group showed peripheral leukopenia, transient hypotension, excess lung water, Increased albumin leakage, PMN accumulation in lung tissue, and gross histopathologic edema. G-CSF-treated animals showed attenuated responses in peripheral leukopenia, excess lung water, and albumin leakage in comparison with the endotoxinalone group. No augmented responses were seen in the G-CSF group. The CPA + endotoxin group also had attenuated lung injury, which was similar to that in the G-CSF group. In conclusion, pretreatment with G-CSF tended to attenuate rather than enhance neutrophil-dependent acute lung responses to endotoxin.