Antimicrobial effects of granulocyte-macrophage colony-stimulating factor in protein-energy malnutrition
A. D. Hill, H. Naama, J. Shou, S. E. Calvano and J. M. Daly
Department of Surgery, New York, NY Hospital-Cornell Medical Center.
OBJECTIVES: 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. DESIGN: Nonblinded study of GM-CSF in mice with
protein-energy malnutrition. SETTING: A university-based surgical
laboratory and animal facility. INTERVENTION: In study 1, malnourished mice
were randomized to receive either GM-CSF (120 micrograms/kg subcutaneously
to receive either GM-CSF (120 micrograms/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 x 10(5) 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 micrograms/mL) for interleukin-4,
interleukin-10, and interferon-gamma production. RESULTS: 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.
CONCLUSIONS: 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.
