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 treatme nts: (I) G-CSF 50 mu g/kg subcutaneously twice daily beginning 2 d pri or to being killed; (2) ANTU 50 mg/kg intraperitoneally; (3) ANTU+G-CS F 50, 25, or 12.5 mu g/kg; (4) HCl 0.6 ml of a 0.1 N solution intratra cheally; (5) HCl+G-CSF 50 or 25 mu g/kg; (6) control solutions. Lung i njury was quantified by measurement of lung wet/dry weights, by histop athologic scoring, and by measurement of fluid flux during ex vivo per fusion. G-CSF pretreatment elevated the baseline blood neutrophil coun ts as much as 6-fold compared with Control, and it increased the numbe rs of lung neutrophils and caused a mild histologic lung injury, but i t did not significantly alter wet/dry weight ratios or fluid flux. ANT U alone and HCl alone caused a moderate histologic lung injury, increa sed wet/dry weight ratio, and resulted in a small increase in flux. Th e combination injuries, ANTU+G-CSF and HCl+G-CSF, caused a more severe lung injury manifested by increased wet/dry weight ratios and increas e in flux when compared with ANTU alone and HCl alone, respectively. W e conclude that pretreatment with G-CSF potentiates ANTU- and HCl-indu ced lung injury in non-neutropenic rats. The potential for G-CSF to ag gravate acute lung injury in patients remains speculative.