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

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.

• Authors: F Dallaire, N Ouellet, M Simard, Y Bergeron, M G Bergeron
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 183 Issue 1 Pg. 70-7 (Jan 01 2001) ISSN: 0022-1899 [Print] United States
• PMID: 11087202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Granulocyte Colony-Stimulating Factor
• Peroxidase

Topics

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