THE EFFECTS OF SEVERE PROTEIN-CALORIE MALNUTRITION ON ANTI-BACTERIAL DEFENSE-MECHANISMS IN THE RAT LUNG

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Abstract
Protein-calorie malnutrition (PCM) impairs systemic immunity in humans and animals, but its effects on regional defense mechanisms in the lung are not clear. Lung phagocytic antibacterial defenses were investigated in vivo and in vitro in an animal model of PCM. Matched groups of weanling rats consumed isocaloric diets containing either 0.8% (PCM) or 24% protein (control, C). A 3rd group of animals was fed the C diet in restricted amounts to match the daily caloric intake of the PCM animals (pair-fed control, PF). After 4 wk on the diet, PCM animals were hypoproteinemic, hypoalbuminemic and anemic and had depressed systemic cell-mediated immunity. In vivo, the lung clearance rate of Listeria monocytogenes was markedly delayed in PCM animals (% bacaterial recovery at 9 days, mean .+-. SE: PCM =120 .+-. 25.1; PF = 5.2 .+-. 3.0; C = 0.6 .+-. 0.6; P < 0.001 for PCM vs. C). Only 36% of the PCM animals survived for 9 days after Listeria exposure; > 94% of the C and PF animals survived (P < 0.01). Recruitment of macrophages to the lungs of PCM animals after Listeria aerosolization was markedly impaired compared with that in the PF and C animals (P < 0.001). Lung clearance rates of 2 pyogenic organisms, Staphylococcus aureus 502a and Pseudomonas aeruginosa 177, were similar in all groups. In vitro, alveolar macrophage chemotaxis toward zymosan-activated serum, and microbicidal activity against S. epidermidis were also similar in all groups of animals. Evidently, in the rat, PCM impairs the pulmonary clearance of L. monocytogenes, and that this defect is associated with impaired macrophage recruitment to the lung after Listeria inhalation. Because Listeria is a prototype for organisms that are cleared from the lung by cell-mediated immune responses, these findings provide insight into the mechanisms that may underlie the pathogenesis of some pulmonary infections in PCM.

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