ObjectiveTo study the therapeutic effect of granulocyte colony-stimulating factor (G-CSF) on the mortality rate and host defense pattern in fulminant intra-abdominal sepsis.DesignProspective, randomized, controlled trial.SettingResearch laboratory in a university hospital.SubjectsAdult male Wistar rats.InterventionsFulminant 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 micro gram/kg/24 hrs), and therapy was started 7 days or 1 day before, or 4 hrs after sepsis induction (n equals 24). To examine alterations in host response pattern, G-CSF (20 micro gram/kg/24 hrs) was given at sepsis induction, and rats were killed 4, 8, 12, and 24 hrs later (n equals 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.Measurements and Main ResultsG-CSF (20 micro gram/kg/24 hrs), given 4 hrs after sepsis induction, reduced the mortality rate from 96% to 42%. Increasing the dose (100 micro gram/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.ConclusionsG-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.(Crit Care Med 1996; 24:820-826)