Effects of granulocyte-colony stimulating factor on the polymorphonuclear leukocyte activity and the course of sepsis in rats with experimental peritonitis.

PURPOSE: Polymorphonuclear leucocytes (PML) play an essential role in the host immune response to severe infections. The effects of granulocyte-colony stimulating factor (G-CSF) on the PML immune functions during serious abdominal infection and course of sepsis, and on the survival in rats with peritonitis are the main subjects of this study.
METHODS: The first phase of the study was carried out on 30 Wistar-albino rats equally divided into three groups; Group 1 (control) sham laparotomy; Group 2 (peritonitis); and Group 3 (peritonitis+G-CSF) with fecal peritonitis created by a cecal puncture. At postoperative hours 3, 12, and 24, 0.5 ml normal saline was injected subcutaneously in groups 1 and 2, and 0.5 ml solution containing 50 microg/kg of G-CSF in group 3. The phagocytic and chemotactic activities of neutrophils and monocytes were evaluated by a flow cytometry analysis. The plasma lactate concentrations were assessed as a marker of tissue perfusion during sepsis. The second phase was a survival analysis, which was observed during 10 days on 20 rats equally divided into two groups; group 1 (peritonitis) and group 2 (peritonitis+G-CSF). 0.5 ml normal saline in group 1 and 50 microg/kg of G-CSF in group 2 was injected subcutaneously at the 3rd hour and twice daily.
RESULTS: Both the neutrophil- (1.636 vs 2.236) and monocyte-related (1.789 vs 2.465) phagocytic activities significantly (P < 0.001) improved after the G-CSF administration in the rats with peritonitis. In addition, the G-CSF treatment significantly (P < 0.0014) improved the chemotactic activity (1.18 vs 2.75) of neutrophils, and partly supported (P < 0.0952) the chemotactic activity (1.69 vs 2.37) of monocytes. The plasma lactate level (1.86 vs 4.9 mmol/l) was significantly (P < 0.0001) increased after septic changes due to experimental peritonitis. On the other hand, the lactate concentration was significantly (P < 0.001) decreased (4.9 vs 2.63 mmol/l) after the G-CSF administration. The survival was 20% at the 4th day and 0 at the 6th day in peritonitis, and 90% at the 4th day (P = 0.0055) and 80% at the 6th day (P = 0.0007) days in the peritonitis+G-CSF groups.
CONCLUSION: G-CSF enhances the immune functions of neutrophils and monocytes. The increased activities of these cells have a beneficial effect on the enhancement of the host immune response during severe infections. The improved immune function of PML due to the G-CSF treatment thus ameliorates the survival and the courses of sepsis, which is also defined by tissue perfusion and the cellular oxygen balance, which is affected by septic changes.