Granulocyte colony-stimulating factor exacerbates the acute lung injury and pulmonary fibrosis induced by intratracheal administration of bleomycin in rats

Exp Toxicol Pathol. 2002 Feb;53(6):501-10. doi: 10.1078/0940-2993-00218.

Abstract

We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on lung injury induced by intratracheal administration of bleomycin (BLM, 2 mg/200 micro1) in rats. In experiment 1, G-CSF (10, 30 and 100 microg/kg/day, s.c.) was administered to rats treated with BLM or saline for 7 days starting immediately after BLM administration. In rats receiving G-CSF alone, a large number of neutrophils were noted in the pulmonary capillaries, although there were no lung lesions. In rats receiving BLM alone, diffuse alveolar damage was observed. The administration of G-CSF to BLM-treated rats increased the total lung lesion per unit of pulmonary parenchyma (total lung lesion %) along with increases in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion in a dose-dependent fashion. In experiment 2, 100 microg/kg/day of G-CSF was administered to rats treated with BLM or saline for up to 28 days starting immediately after BLM administration. The administration of 100 microg/kg/day of G-CSF to BLM-treated rats showed no effects at 14 days but it increased the lung lesion % and the score of lung fibrosis along with the increase in the number of neutrophils infiltrating in the pulmonary lesion at 28 days. These findings suggest that G-CSF administration to BLM-treated rats influenced and exacerbated the BLM-induced acute lung injury, and also exacerbated pulmonary fibrosis in a dose-dependent fashion. The exacerbation of lung injury coincided with the marked increase in the peripheral neutrophil count and the number of neutrophils infiltrating in the pulmonary lesion.

MeSH terms

  • Acute Disease
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / toxicity*
  • Bleomycin / administration & dosage
  • Bleomycin / toxicity*
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Injections, Subcutaneous
  • Intubation, Intratracheal
  • Leukocyte Count
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Organ Size / drug effects
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / mortality
  • Pulmonary Fibrosis / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Survival Rate

Substances

  • Antibiotics, Antineoplastic
  • Recombinant Proteins
  • Bleomycin
  • Granulocyte-Macrophage Colony-Stimulating Factor