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 studied using guinea pigs. Animals were divided into four groups: (1) saline control, (2) endotoxin alone, (3) cyclophosphamide (CPA) + endotoxin, and (4) CPA + rG-CSF + endotoxin. CPA was injected intraperitoneally to suppress hematopoietic function 7 d before the study, rG-CSF at a dose of 100 mu g/kg was administered subcutaneously twice a day for 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 mixed with saline or endotoxin to obtain a lobar distribution. Lung injury 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 also counted the number of neutrophils in bronchoalveolar lavage (BAL) fluid and fixed lung tissues. T/P, but not W/D, increased in endotoxin-alone and CPA + endotoxin groups compared with the saline control group (p < 0.01). Both T/P and W/D of the CPA + rG-CSF + endotoxin group were significantly higher than those of the endotoxin-alone and CPA + endotoxin groups (p < 0.01). In the CPA + rG-CSF + endotoxin group, histopathologic examination of the lung sections showed neutrophil recruitment into the lung, and neutrophil. counts in BAL fluid were elevated. In conclusion, pretreatment with rG-CSF increased sequestration of neutrophils into the lung and exacerbated the lung injury induced by intratracheal endotoxin in CPA-treated guinea pigs.