ANTIMICROBIAL EFFECTS OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PROTEIN-ENERGY MALNUTRITION

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.