Impaired macrophage function in severe protein-energy malnutrition
H. P. Redmond, P. Leon, M. D. Lieberman, K. Hofmann, J. Shou, J. V. Reynolds, J. Goldfine, R. B. Johnston Jr and J. M. Daly
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia.
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-Guerin). 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-Guerin 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.
