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 i noculations were 10(7) cfu/mouse (high inoculum) and 5 x 10(4) cfu/mouse (l ow inoculum) of Streptococcus pneumoniae, which induced severe or mild lung inflammation, respectively. With the low inoculum, rhG-CSF significantly i mproved survival when initiated 24 h or 10 min before, but not when initiat ed 24 h after, infection. Pretreatment with rhG-CSF significantly increased myeloperoxidase (MPO) activity in lungs 8 h after the infection and increa sed circulating neutrophil count 24, 48, and 72 h after infection. In contr ast, rhG-CSF did not improve survival of animals infected with the high ino culum and did not increase MPO activity or neutrophil count in blood over t hose 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.