title: Neutrophil stimulation with granulocyte colony-stimulating factor worsens ventilator-induced lung injury and mortality in rats.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Friedrich-Schiller-University Hospital, Jena, Germany. ana@zentralklinik-bad-berka.de
authors.forename: Waheedullah
authors.initials: W
authors.lastname: Karzai
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.forename: Norbert
authors.initials: N
authors.lastname: Heinicke
authors.forename: Christian
authors.initials: C
authors.lastname: Niemann
authors.forename: Eric P
authors.initials: EP
authors.lastname: Gerstenberger
authors.forename: Rosaly
authors.initials: R
authors.lastname: Correa
authors.forename: Steven
authors.initials: S
authors.lastname: Banks
authors.forename: Bjoern
authors.initials: B
authors.lastname: Mehlhorn
authors.forename: Frank
authors.initials: F
authors.lastname: Bloos
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinhart
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002404:Catheterization; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D010243:Paralysis / Q000139:chemically induced; D011134:Polysaccharides / Q000494:pharmacology; D011654:Pulmonary Edema / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000401:mortality*; D012129:Respiratory Function Tests; D013268:Stimulation, Chemical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D011134:Polysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; C007789:fucoidan