To evaluate, in a murine model of protein-energy malnutrition, whether granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the host response to a septic challenge and to determine the potential mechanisms involved.
Nonblinded study of GM-CSF in mice with protein-energy malnutrition.
A university-based surgical laboratory and animal facility.
In study 1, malnourished mice were randomized to receive either GM-CSF (120 μg/kg subcutaneously from day 4 to 7 of the protein-free diet) or saline vehicle as a control. On day 7, all mice were given Candida albicans (5×105 organisms intravenously). In study 2, malnourished mice received the same dose of GM-CSF or saline vehicle for 7 days of the protein-free diet.
Main Outcome Measures:
In study 1 mice were followed up for survival. In study 2, after 7 days of diets, splenic macrophages were harvested and were assayed for interleukin-6, superoxide anion, and nitric oxide production. Splenocytes were stimulated with concanavalin A (5 μg/mL) for interleukin-4, interleukin-10, and interferon-γ production.
Treatment with GM-CSF significantly enhanced survival in malnourished mice infected with C albicans. Treatment with GM-CSF was associated with increased production from splenic macrophages of interleukin-6, superoxide anion, and nitric oxide as well as decreased interleukin-4 production from splenocytes.
This study suggests a beneficial role for GM-CSF in the malnourished host predisposed to infection. The antimicrobial properties of GM-CSF may function through enhanced production of nitric oxide and superoxide anion.(Arch Surg. 1995;130:1273-1278)