Granulocyte colony-stimulating factor improves myelopoiesis and host defense in fulminant intra-abdominal sepsis in rats.
The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) was studied in a model of fulminant sepsis in rats. Polymicrobial peritonitis was induced by a 4 mm cecal perforation and 10 micrograms/kg recombinant human G-CSF was given intravenously every 12 h, with the first dose at sepsis induction or 4 h post-induction. Rats were sacrificed at various intervals throughout sepsis to measure levels of neutrophil progenitors in the bone marrow and neutrophils and bacteria in blood and peritoneal fluid. Sepsis gave a sustained neutropenia and bacteremia, but did not affect numbers of blast- or GM-colonies, and only a delayed and moderate proliferation of G-clones was seen. Treatment with G-CSF at sepsis induction improved myelopoiesis by doubling the numbers of GM- and G-progenitors at 12 and 24 h post-induction. Concentrations of neutrophils increased twofold in blood and 5-fold in peritoneal fluid, while bacteria counts in the same compartments declined logarithmically. Mortality was 92% in untreated sepsis and declined to 46% when G-CSF therapy was started at sepsis induction, and to 42% following 4 h delayed therapy.
Lundblad
R
R
Norwegian Radium Hospital, Oslo.
Wang
M Y
MY
Kvalheim
G
G
Lingaas
E
E
Giercksky
K E
KE
D000208:Acute Disease; D000818:Animals; D015169:Colony Count, Microbial; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils; D010538:Peritonitis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013234:Stem Cells
D016179:Granulocyte Colony-Stimulating Factor