Efficacy of recombinant human granulocyte colony-stimulating factor in a murine model of pneumococcal pneumonia: effects of lung inflammation and timing of treatment

J Infect Dis. 2001 Jan 1;183(1):70-7. doi: 10.1086/317652. Epub 2000 Nov 15.

Abstract

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a murine model of pneumococcal pneumonia was examined. Intranasal inoculations were 10(7) cfu/mouse (high inoculum) and 5 x 10(4) cfu/mouse (low inoculum) of Streptococcus pneumoniae, which induced severe or mild lung inflammation, respectively. With the low inoculum, rhG-CSF significantly improved survival when initiated 24 h or 10 min before, but not when initiated 24 h after, infection. Pretreatment with rhG-CSF significantly increased myeloperoxidase (MPO) activity in lungs 8 h after the infection and increased circulating neutrophil count 24, 48, and 72 h after infection. In contrast, rhG-CSF did not improve survival of animals infected with the high inoculum and did not increase MPO activity or neutrophil count in blood over those of sham-treated controls. These data strongly suggest that the severe inflammatory response typically observed in pneumococcal pneumonia recruits a maximum number of neutrophils in the lungs and thus masks the beneficial effect of rhG-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Leukocyte Count
  • Lung / drug effects*
  • Lung / immunology
  • Lung / metabolism
  • Mice
  • Neutrophils / immunology
  • Peroxidase / metabolism
  • Pneumonia, Pneumococcal / blood
  • Pneumonia, Pneumococcal / drug therapy*
  • Pneumonia, Pneumococcal / metabolism
  • Streptococcus pneumoniae*
  • Time Factors

Substances

  • Granulocyte Colony-Stimulating Factor
  • Peroxidase