Adk. Hill et al., ANTIMICROBIAL EFFECTS OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PROTEIN-ENERGY MALNUTRITION, Archives of surgery, 130(12), 1995, pp. 1273-1278
Objectives: To evaluate, in a murine model of protein-energy malnutrit
ion, 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 sur
gical laboratory and animal facility. Intervention: In study 1, malnou
rished mice were randomized to receive either GM-CSF (120 mu g/kg subc
utaneously 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 th
e 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 sur
vival. In study 2, after 7 days of diets, splenic macrophages were har
vested and were assayed for interleukin-6, superoxide anion, and nitri
c oxide production. Splenocytes were stimulated with concanavalin A (5
mu g/mL) for interleukin-4, interleukin-10, and interferon-gamma prod
uction. 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 i
nterleukin-6, superoxide anion, and nitric oxide as well as decreased
interleukin-4 production from splenocytes. Conclusions: This study sug
gests a beneficial role for GM-CSF in the malnourished host predispose
d to infection. The antimicrobial properties of GM-CSF may function th
rough enhanced production of nitric oxide and superoxide anion.