Am. J. Respir. Crit. Care Med., Volume 159, Number 5, May 1999, 1377-1382

G-CSF during Escherichia coli versus Staphylococcus aureus Pneumonia in Rats Has Fundamentally Different and Opposite Effects

WAHEEDULLAH KARZAI, BERND ULRICH von SPECHT, CHANTAL PARENT, J. HABERSTROH, KARIN WOLLERSEN, CHARLES NATANSON, STEVEN M. BANKS, and PETER. Q. EICHACKER

Departments of Anesthesiology and Surgical Research, University Hospital, Freiburg, Germany; and Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland

We investigated if bacteria type alters outcome with prophylactic granulocyte colony stimulating factor (G-CSF) therapy during pneumonia. Rats received G-CSF or placebo daily for 6 d and after the third dose were intrabronchially inoculated with either Escherichia coli or Staphylococcus aureus. Without G-CSF, E. coli and S. aureus produced similar (p = NS) mortality rates (36 versus 38%) and serial changes in mean circulating neutrophil counts (CNC), 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 greater than 20-fold decrease in mean (± SE) CNC (× 10³/ mm³) to below placebo (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 placebo (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, G-CSF improved oxygenation and decreased bacteremia and mortality (G-CSF therapy, E. coli versus S. 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 clearance, resulting in less pulmonary injury and decreased death. During E. coli pneumonia with high TNF levels, G-CSF paradoxically decreased CNC, resulting in impaired bacterial clearance and worsened pulmonary injury and death. Bacterial species and the associated inflammatory mediator response can alter outcome with prophylactic G-CSF therapy during pneumonia.

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