Deleterious Effects of Mild Hypothermia in Septic Rats Are Ameliorated by Granulocyte Colony-stimulating Factor

Abstract

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 (32°C) was compared with normothermia (38°C), 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 (32°C), normothermia, and postoperative hypothermia (32°C) with 20 μg/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 μg/ml; hypothermia plus G-CSF group, 247 ± 51 pg/ml) and macrophage inflammatory protein-2 (hypothermia group, 239 ± 43 μg/ml; hypothermia plus G-CSF group, 178 ± 21 μg/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.