GRANULOCYTE-COLONY-STIMULATING FACTOR IMPROVES SURVIVAL RATE AND REDUCES CONCENTRATIONS OF BACTERIA, ENDOTOXIN, TUMOR-NECROSIS-FACTOR, AND ENDOTHELIN-1 IN FULMINANT INTRAABDOMINAL SEPSIS IN RATS

Objective: To study the therapeutic effect of granulocyte colony-stimu lating factor (G-CSF) on the mortality rate and host defense pattern i n fulminant intra abdominal sepsis. Design: Prospective, randomized, c ontrolled trial. Setting: Research laboratory in a university hospital . Subjects: Adult male Wistar rats. Interventions: Fulminant polymicro bial intra-abdominal sepsis was induced by a 4-mm cecal perforation. S urvival experiments were performed with two different doses of G-CSF ( 20 and 100 mu g/kg/24 hrs), and therapy was started 7 days or 1 day be fore, or 4 hrs after sepsis induction (n = 24). To examine alterations in host response pattern, G-CSF (20 mu g/kg/24 hrs) was given at seps is induction, and rats were killed 4, 8, 12, and 24 hrs later (n = 8-1 6 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 l actate were determined. Measurements and Main Results: G-CSF (20 mu g/ kg/24 hrs), given 4 hrs after sepsis induction, reduced the mortality rate from 96% to 42%. Increasing the dose (100 mu g/kg/24 hrs), or giv ing G-CSF as prophylaxis (starting 7 days or 1 day before sepsis), gav e no further protection. G-CSF attenuated the sepsis-induced en hancem ent of circulating bacteria, endotoxin, TNF, and endothelin-1, resulti ng in improved fluid balance and reduced lactate concentration. No his topathologic alterations were observed after G-CSF treatment. Conclusi ons: G-CSF improves host defense and survival rate in experimentally i nduced fulminant intra abdominal sepsis. Clearance of bacteria and end otoxin is improved, concentrations of TNF and endothelin-1 are suppres sed, and microvascular flow is improved. G CSF does not induce neutrop hil-mediated tissue damage.