Antimicrobial effects of granulocyte-macrophage colony-stimulating factor in protein-energy malnutrition.
OBJECTIVE
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.


METHODS
Nonblinded study of GM-CSF in mice with protein-energy malnutrition.


METHODS
A university-based surgical laboratory and animal facility.


METHODS
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.


METHODS
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.
D000818:Animals; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D011502:Protein-Energy Malnutrition / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism
D016207:Cytokines; D013481:Superoxides; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor