Effects of granulocyte colony-stimulating factor (G-CSF) on bleomycin-induced lung injury of varying severity

Toxicol Pathol. 2003 Nov-Dec;31(6):665-73. doi: 10.1080/01926230390244924.

Abstract

We evaluated the effects of granulocyte colony-stimulating factor (G-CSF) on bleomycin (BLM)-induced lung injury that developed diffuse alveolar damage and subsequent pulmonary fibrosis (PF) of varying severity. G-CSF (100 microg/kg/day) was administered subcutaneously to BLM (0.2, 20, 2,000 microg)-treated or -untreated rats for 3 or 14 days. In the BLM 0.2 microg group, slight alveolar mononuclear cell infiltration was observed, although PF was not noted. In the BLM 20-microg and 2,000-microg groups, diffuse alveolar damage along with neutrophil infiltration and subsequent PF were observed. In the saline + G-CSF group and BLM 0.2 microg + G-CSF group, a marked increase in the number of alkaline phosphatase (ALP)-positive neutrophils was noted in the alveolar capillaries, although there was neither neutrophil infiltration in alveoli nor exacerbation of lung injury. In the BLM 20 microg + G-CSF and BLM 2,000 microg + G-CSF groups, an exacerbation of lung injury along with an increase in the number of ALP-positive neutrophils in the alveoli was observed. These results indicate that the administration of G-CSF to rats with slight lung injury bearing no PF does not exacerbate the lung injury. The exacerbating effects of G-CSF seem to be associated not only with the marked infiltration of activated neutrophils but also with the severity of underlying lung injury.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bleomycin / administration & dosage
  • Bleomycin / toxicity*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Injections, Subcutaneous
  • Intubation, Intratracheal
  • Male
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Neutrophils / pathology
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / pathology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Bleomycin
  • Granulocyte Colony-Stimulating Factor
  • Alkaline Phosphatase