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 micrograms/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, [125I]albumin leakage in lung tissue, and histopathologic features were examined at 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 endotoxin-alone 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.
Kanazawa
M
M
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Ishizaka
A
A
Hasegawa
N
N
Suzuki
Y
Y
Yokoyama
T
T
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D004731:Endotoxins / Q000009:adverse effects*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects*; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000517:prevention & control
D004731:Endotoxins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide