Effect of granulocyte colony-stimulating factor on acute lung injury in the rat.
The effect of G-CSF pretreatment on experimental acute lung injury was studied in Sprague-Dawley rats receiving one of the following treatments: (1) G-CSF 50 micrograms/kg subcutaneously twice daily beginning 2 d prior to being killed; (2) ANTU 50 mg/kg intraperitoneally; (3) ANTU+G-CSF 50, 25, or 12.5 micrograms/kg; (4) HCl 0.6 ml of a 0.1 N solution intratracheally; (5) HCl+G-CSF 50 or 25 micrograms/kg; (6) control solutions. Lung injury was quantified by measurement of lung wet/dry weights, by histopathologic scoring, and by measurement of fluid flux during ex vivo perfusion. G-CSF pretreatment elevated the baseline blood neutrophil counts as much as 6-fold compared with Control, and it increased the numbers of lung neutrophils and caused a mild histologic lung injury, but it did not significantly alter wet/dry weight ratios or fluid flux. ANTU alone and HCl alone caused a moderate histologic lung injury, increased wet/dry weight ratio, and resulted in a small increase in flux. The combination injuries, ANTU+G-CSF and HCl+G-CSF, caused a more severe lung injury manifested by increased wet/dry weight ratios and increase in flux when compared with ANTU alone and HCl alone, respectively. We conclude that pretreatment with G-CSF potentiates ANTU- and HCl-induced lung injury in non-neutropenic rats. The potential for G-CSF to aggravate acute lung injury in patients remains speculative.
King
J
J
Department of Medicine, Louisiana State University Medical School, New Orleans.
Deboisblanc
B P
BP
Mason
C M
CM
Onofrio
J M
JM
Lipscomb
G
G
Mercante
D E
DE
Summer
W R
WR
Nelson
S
S
D000818:Animals; D001794:Blood Pressure; D002199:Capillary Permeability; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D009504:Neutrophils; D009929:Organ Size; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016179:Granulocyte Colony-Stimulating Factor