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.
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.
Lundblad
R
R
Norwegian Radium Hospital and Institute for Cancer Research, Oslo, Norway.
Nesland
J M
JM
Giercksky
K E
KE
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*
D016232:Endothelins; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor