G-CSF during Escherichia coli versus Staphylococcus aureus pneumonia in rats has fundamentally different and opposite effects

We investigated if bacteria type alters outcome with prophylactic granulocy te colony stimulating factor (G-CSF) therapy during pneumonia. Rats receive d G-CSF or placebo daily for 6 d and after the third dose were intrabronchi ally inoculated with either Escherichia coli or Staphylococcus aureus. With out G-CSF, E. coli and S. aureus produced similar (p = NS) mortality rates (36 versus 38%) and serial changes in mean circulating neutrophil counts (C NC), but differing mean (+/-SE) tumor necrosis factor (TNF) levels (E. coli , 259 +/- 104 versus S. aureus, 51 +/- 17 pg/ml, p = 0.01). G-CSF prior to bacteria increased mean CNC more than six times compared with placebo (p = 0.001). However, with G-CSF in the first 6 h after E. coli, there was a gre ater than 20-fold decrease in mean (+/- SE) CNC (x 10(3)/mm(3)) to below pl acebo (0.5 +/- 0.1 versus 0.8 +/- 0.1), whereas with G-CSF after S. aureus, there was only a fivefold decrease in mean CNC and CNC were greater than p lacebo (1.8 +/- 0.2 versus 0.8 +/- 0.1) (E. coli versus S. aureus decrease in CNC with G-CSF, p = 0 001). With E. coli, G-CSF worsened oxygenation and increased bacteremia and mortality, whereas with S. aureus, C-CSF improved oxygenation and decreased bacteremia and mortality (G-CSF therapy, E. coli versus 5. aureus, p = 0.03, 0.05, and 0.001, respectively). Thus, during S . aureus pneumonia with low TNF levels, G-CSF increased CNC and bacterial c learance, resulting in less pulmonary injury and decreased death. During E. coli pneumonia with high TNF levels, G-CSF paradoxically decreased CNC, re sulting in impaired bacterial clearance and worsened pulmonary injury and d eath. Bacterial species and the associated inflammatory mediator response c an alter outcome with prophylactic C-CSF therapy during pneumonia.