The effects of severe protein-calorie malnutrition on antibacterial defense mechanisms in the rat lung

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. Therefore, we investigated lung phagocytic antibacterial defenses 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 third 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 (% bacterial recovery at 9 days, mean +/- SE:PCM = 120 +/- 25.1; PF = 5.2 +/- 3.0; C = 0.6 +/- 0.6; p less than 0.001 for PCM versus C). Only 36% of the PCM animals survived for 9 days after Listeria exposure, whereas more than 94% of the C and PF animals survived (p less than 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 less than 0.001). By contrast, 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 Staphylococcus epidermidis were also similar in all groups of animals. Our findings indicate that 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.(ABSTRACT TRUNCATED AT 250 WORDS)