Neutrophil stimulation with granulocyte colony-stimulating factor worsens ventilator-induced lung injury and mortality in rats

Anesthesiology. 2005 Nov;103(5):996-1005. doi: 10.1097/00000542-200511000-00014.


Background: Based on the association between the neutrophil and ventilator-induced lung injury, the authors hypothesized that neutrophil inhibition with fucoidin would be beneficial and stimulation with granulocyte colony-stimulating factor (G-CSF) would be harmful in a rat model of lethal ventilator-induced lung injury.

Methods: Animals (n = 111) were randomly assigned to be pretreated with fucoidin, G-CSF, or placebo (control) before 4 h of low-tidal-volume (10 ml/kg) or high-tidal-volume (40 ml/kg) mechanical ventilation.

Results: All low-volume animals survived. With high volumes, compared with controls, fucoidin did not improve survival (3 of 20 control animals and 5 of 20 fucoidin animals died; P = 0.51) but G-CSF significantly worsened it (18 of 22 animals died; P < 0.001). Circulating neutrophils were increased early with G-CSF and late with fucoidin with low and high tidal volumes (P < 0.05 for each treatment and tidal volume). Fucoidin decreased lung neutrophils, but these were only significant with high tidal volumes, whereas G-CSF increased lung neutrophils but only significantly with low tidal volumes (P < or = 0.01 for each). Fucoidin did not alter any cardiopulmonary measure significantly. Compared with control, G-CSF increased airway pressures with high tidal volumes and worsened lung edema and arterial oxygen with both tidal volumes (P < 0.05 for each).

Conclusions: In this model, neutrophil stimulation by G-CSF increased lung dysfunction and with high tidal volumes worsened survival rates. Extrapolated clinically, neutrophil stimulation either by agents such as G-CSF or conditions such as sepsis may aggravate ventilator-induced lung injury.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bronchoalveolar Lavage Fluid / cytology
  • Catheterization
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hemodynamics / drug effects
  • Interleukin-6 / metabolism
  • Leukocyte Count
  • Lung / pathology
  • Lung Diseases / mortality
  • Lung Diseases / physiopathology
  • Lung Diseases / prevention & control*
  • Male
  • Neutrophils / drug effects*
  • Neutrophils / pathology
  • Paralysis / chemically induced
  • Polysaccharides / pharmacology
  • Pulmonary Edema / pathology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins
  • Respiration, Artificial / adverse effects*
  • Respiration, Artificial / mortality*
  • Respiratory Function Tests
  • Stimulation, Chemical
  • Tumor Necrosis Factor-alpha / metabolism
  • Ventilators, Mechanical / adverse effects*


  • Anti-Bacterial Agents
  • Interleukin-6
  • Polysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor
  • fucoidan