title: Granulocyte colony-stimulating factor improves survival rate and reduces concentrations of bacteria, endotoxin, tumor necrosis factor, and endothelin-1 in fulminant intra-abdominal sepsis in rats.
abstract: OBJECTIVE
  To study the therapeutic effect of granulocyte colony-stimulating factor (G-CSF) on the mortality rate and host defense pattern in fulminant intra-abdominal sepsis.
  
  
  METHODS
  Prospective, randomized, controlled trial.
  
  
  METHODS
  Research laboratory in a university hospital.
  
  
  METHODS
  Adult male Wistar rats.
  
  
  METHODS
  Fulminant polymicrobial intra-abdominal sepsis was induced by a 4-mm cecal perforation. Survival experiments were performed with two different doses of G-CSF (20 and 100 microg/kg/24 hrs), and therapy was started 7 days or 1 day before, or 4 hrs after sepsis induction (n = 24). To examine alterations in host response pattern, G-CSF (20 microg/kg/24 hrs) was given at sepsis induction, and rats were killed 4, 8, 12 and 24 hrs later (n = 8-16 per time period). Histologic examination of lung, liver, spleen, and kidney was performed, and blood concentrations of bacteria, endotoxin, tumor necrosis factor (TNF), endothelin-1, packed cell volume, and lactate were determined.
  
  
  RESULTS
  G-CSF (20 microg/kg/24 hrs), given 4 hrs after sepsis induction, reduced the mortality rate from 96% to 42%. Increasing the dose (100 micrograms/kg/24 hrs), or giving G-CSF as prophylaxis (starting 7 days or 1 day before sepsis), gave no further protection. G-CSF attenuated the sepsis-induced enhancement of circulating bacteria, endotoxin, TNF, and endothelin-1, resulting in improved fluid balance and reduced lactate concentration. No histopathologic alterations were observed after G-CSF treatment.
  
  
  CONCLUSIONS
  G-CSF improves host defense and survival rate in experimentally induced fulminant intra-abdominal sepsis. Clearance of bacteria and endotoxin is improved, concentrations of TNF and endothelin-1 are suppressed, and microvascular flow is improved. G-CSF does not induce neutrophil-mediated tissue damage.
authors.affiliation: Norwegian Radium Hospital and Institute for Cancer Research, Oslo, Norway.
authors.forename: R
authors.initials: R
authors.lastname: Lundblad
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: K E
authors.initials: KE
authors.lastname: Giercksky
mesh_terms: D000818:Animals; D002429:Cecal Diseases / Q000150:complications*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016232:Endothelins / Q000097:blood*; D004731:Endotoxins / Q000097:blood*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007416:Intestinal Perforation / Q000150:complications*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016232:Endothelins; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor