Abstract
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.
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