The beneficial effects of immunostimulation in posttraumatic sepsis

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a myelopoietic cytokine that may enhance immune mechanisms directed against bacterial infection. Injury is associated with an increased incidence of such infection. This study assessed the potential immunostimulatory role of GM-CSF in the injured host predisposed to infection. Six- to eight-week-old female CD-1 mice underwent trauma and were then randomized to receive either GM-CSF or saline vehicle control intraperitoneally for 5 days. They then received a septic challenge in the form of a cecal ligation and puncture. Following this, assessment was made of survival and bacterial growth indices in blood cultures, and peritoneal cells were harvested for assessment of peritoneal immune function. Intraperitoneal GM-CSF administration daily for 5 days following injury was associated with significantly greater survival following cecal ligation and puncture compared to controls (40 vs 5%, P < 0.05). There was a significant increase in peritoneal cell yields in the GM-CSF group compared to the control group (11 ± 1 × 10⁶ vs 8 ± 1 × 10⁶P < 0.05). PMA-stimulated macrophages released significantly higher amounts of both superoxide anion (1.4 ± 0.1 vs 0.93 ± 0.1, P < 0.05) and tumor necrosis factor (5.2 ± 0.6 vs 2.6 ± 0.7, P < 0.03) and significantly less nitric oxide compared to the control group (175 ± 8 vs 267 ± 24, P < 0.003). Finally, bacterial growth indices were significantly reduced following GM-CSF administration (194 ± 6 vs 218 ± 4, P < 0.01). In conclusion, administration of GM-CSF following injury is protective against the development of lethal intraabdominal sepsis.