Deleterious effects of mild hypothermia in septic rats are ameliorated by granulocyte colony-stimulating factor

Background: The authors studied the effects of mild hypothermia on the outcome in a rat model of intraabdominal sepsis and tested whether granulocyte colony-stimulating factor (G-CSF) augments the host response and improves outcome during mild hypothermia. Methods: A rat model of peritoneal contamination and infection with human stool bacteria was used to simulate clinical trials that included increasing complexity. In trial 1, postoperative hypothermia (32degreesC) was compared with normothermia (38degreesC), without supportive treatment (10 rats per group). In trial 2, with a more severe infection, rats were given antibiotic prophylaxis. Using 20 rats per group, the authors compared postoperative hypothermia (32degreesC), normothermia, and postoperative hypothermia (32degreesC) with 20 mug/kg G-CSF prophylaxis given 12 h before surgery and 12 h and 36 h after surgery. The primary endpoint was death at 120 h. Secondary endpoints were systemic cytokine concentrations, leukocyte counts, and the phagocytic activity of granulocytes and monocytes. Results: In trial 1, 50% of the normothermia group and 10% of the postoperative hypothermia group survived. In trial 2, 50% of the normothermia group, 20% of the hypothermia group, and 60% of the hypothermia plus G-CSF group survived. Postoperative hypothermia plus G-CSF reduced plasma concentrations of interleukin-6 (hypothermia group, 511 +/- 104 pg/ml; hypothermia plus G-CSF group, 247 +/- 51 pg/ml) and macrophage inflammatory protein-2 (hypothermia group, 239 +/- 43 pg/ml; hypothermia plus G-CSF group, 178 +/- 21 pg/ml). Conclusions: In this rat model of intraabdominal sepsis, postoperative hypothermia was deleterious. However, G-CSF treatment, initiated before contamination, reduced the mortality rate, increased the neutrophil count, and downgraded the systemic cytokine response.