GRANULOCYTE-COLONY-STIMULATING FACTOR IMPROVES MYELOPOIESIS AND HOST-DEFENSE IN FULMINANT INTRAABDOMINAL SEPSIS IN RATS

The therapeutic efficacy of granulocyte colony-stimulating factor (G-C SF) was studied in a model of fulminant sepsis in rats, Polymicrobial peritonitis was induced by a 4 mm cecal perforation and 10 mu g/kg rec ombinant human G-CSF was given intravenously every 12 h, with the firs t dose at sepsis induction or 4 h post-induction, Rats were sacrificed at various intervals throughout sepsis to measure levels of neutrophi l progenitors in the bone marrow and neutrophils and bacteria in blood and peritoneal fluid. Sepsis gave a sustained neutropenia and bactere mia, but did not affect numbers of blast- or GM-colonies, and only a d elayed and moderate proliferation of G-clones was seen. Treatment with G-CSF at sepsis induction improved myelopoiesis by doubling the numbe rs of GM- and G-progenitors at 12 and 24 h post-induction. Concentrati ons of neutrophils increased twofold in blood and 5-fold in peritoneal fluid, while bacteria counts in the same compartments declined logari thmically. Mortality was 92% in untreated sepsis and declined to 46% w hen G-CSF therapy was started at sepsis induction, and to 42% followin g 4 h delayed therapy.