Granulocyte colony-stimulating factor exacerbates acute lung injury induced by intratracheal endotoxin in guinea pigs

Takeshi Terashima, Minoru Kanazawa, Kouichi Sayama, Akitoshi Ishizaka, Tetsuya Urano, Fumio Sakamaki, Hidetoshi Nakamura, Yasuhiro Waki, Sadatomo Tasaka

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Abstract

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 μg/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. 99mTc-labeled macroaggregated albumin was mixed with saline or endotoxin to obtain a lobar distribution. Lung injury was assessed by the concentration ratio of 125I- 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.

Original languageEnglish
Pages (from-to)1295-1303
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume149
Issue number5
DOIs
Publication statusPublished - 1994 May

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Terashima, T., Kanazawa, M., Sayama, K., Ishizaka, A., Urano, T., Sakamaki, F., Nakamura, H., Waki, Y., & Tasaka, S. (1994). Granulocyte colony-stimulating factor exacerbates acute lung injury induced by intratracheal endotoxin in guinea pigs. American journal of respiratory and critical care medicine, 149(5), 1295-1303. https://doi.org/10.1164/ajrccm.149.5.7513596