Efficacy of recombinant human granulocyte colony-stimulating factor in a murine model of pneumococcal pneumonia: effects of lung inflammation and timing of treatment.
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.
Dallaire
F
F
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Département de Microbiologie, Faculté de Médecine, Université Laval, Sainte-Foy, Canada.
Ouellet
N
N
Simard
M
M
Bergeron
Y
Y
Bergeron
M G
MG
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D013296:Streptococcus pneumoniae; D013997:Time Factors
D016179:Granulocyte Colony-Stimulating Factor; D009195:Peroxidase