GRANULOCYTE-COLONY-STIMULATING FACTOR EXACERBATES ACUTE LUNG INJURY-INDUCED BY INTRATRACHEAL ENDOTOXIN IN GUINEA-PIGS

The effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on the lung injury induced by intratracheal endotoxin were s tudied using guinea pigs. Animals were divided into four groups: (1) s aline control, (2) endotoxin alone, (3) cyclophosphamide (CPA) + endot oxin, and (4) CPA + rG-CSF + endotoxin. CPA was injected intraperitone ally to suppress hematopoietic function 7 d before the study, rG-CSF a t a dose of 100 mu g/kg was administered subcutaneously twice a day fo r 5 consecutive d beginning 2 d after the CPA pretreatment. Saline or 0.2 mg/kg of endotoxin was administered via the airway and the animals were observed for 4 h. Tc-99m-labeled macroaggregated albumin was mix ed with saline or endotoxin to obtain a lobar distribution. Lung injur y was assessed by the concentration ratio of I-125-labeled albumin in lung tissue to plasma (T/P) and lung wet-dry weight ratio (W/D). We al so counted the number of neutrophils in bronchoalveolar lavage (BAL) f luid and fixed lung tissues. T/P, but not W/D, increased in endotoxin- alone and CPA + endotoxin groups compared with the saline control grou p (p < 0.01). Both T/P and W/D of the CPA + rG-CSF + endotoxin group w ere significantly higher than those of the endotoxin-alone and CPA + e ndotoxin groups (p < 0.01). In the CPA + rG-CSF + endotoxin group, his topathologic examination of the lung sections showed neutrophil recrui tment into the lung, and neutrophil. counts in BAL fluid were elevated . In conclusion, pretreatment with rG-CSF increased sequestration of n eutrophils into the lung and exacerbated the lung injury induced by in tratracheal endotoxin in CPA-treated guinea pigs.