Impaired macrophage function in severe protein-energy malnutrition.
Protein-energy malnutrition induces immunosuppression that predisposes to sepsis, but the mechanisms are unclear. This study examines the role of the macrophage in host defense in the malnourished state. Swiss-Webster mice (N = 300) were randomly allocated to control (24% casein) or low-protein (2.5% casein) diets for 8 weeks. We studied the ability of two populations of macrophages, peritoneal macrophages, and Kupffer cells to produce superoxide anion after in vivo administration of endotoxin or mycobacterium (bacille Calmette-Guérin). Phorbol diester and Candida albicans were used as stimuli. In another group of mice, we evaluated the ability of interferon gamma to up-regulate superoxide anion release and Candida phagocytosis and killing. Mice under protein-energy malnutrition demonstrated decreased mean body weights, serum protein levels, and cell yields. Superoxide anion production in resident and activated (lipopolysaccharide, interferon gamma, bacille Calmette-Guérin infection) peritoneal macrophages was significantly reduced in the malnourished group. Candida phagocytosis and killing were also both depressed in malnourished mice. Kupffer cells failed to generate superoxide anion in all groups. We conclude that severe protein-energy malnutrition significantly impairs macrophage function, which could diminish response to acute and chronic septic challenges. Interferon gamma up regulated peritoneal macrophage and Kupffer cell microbicidal function, which suggests a therapeutic role for this lymphokine in the malnourished septic host.
Redmond
H P
HP
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia.
Leon
P
P
Lieberman
M D
MD
Hofmann
K
K
Shou
J
J
Reynolds
J V
JV
Goldfine
J
J
Johnston
R B
RB
Daly
J M
JM
D000818:Animals; D002176:Candida albicans / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009163:Mycobacterium bovis / Q000502:physiology; D010529:Peritoneal Cavity / Q000473:pathology; D010587:Phagocytosis; D011502:Protein-Energy Malnutrition / Q000276:immunology / Q000473:pathology*; D013481:Superoxides / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D013481:Superoxides; D007371:Interferon-gamma