Effect of fetal protein malnutrition on the postnatal structure and function of alveolar macrophages.

To test the hypothesis that intrauterine malnutrition may alter ontogeny of the host defense system, an animal model of fetal protein deprivation was developed. Young adult female rats were fed either a deficient (8% protein) diet or a normal (25% protein) diet for 10 days before insemination and throughout gestation. Offspring of the malnourished animals showed significant growth retardation and were hypoproteinemic. Lavageable pulmonary cells from both groups of neonates were similar with respect to number (2.05 x 10(5) cells per animal), type (95% macrophages), size (approximately 10-micrometer diameter), ultrastructure, and presence of surface receptors for IgG. Despite these similarities, alveolar macrophages from malnourished neonates were significantly impaired in their ability both to ingest and to kill Candida tropicalis. Nutritional supplementation of nursing females reversed these functional macrophage defects in their offspring by the time that weaning occurred. These data indicate that fetal protein malnutrition affects macrophage function but that with postnatal nutritional supplementation these defects are rapidly reversed.

Depressed blood neutrophil response to lithium stimulation in newborn rats.

The blood neutrophil response to lithium chloride challenge was determined in one-day-old and young adult rats to test the hypothesis that granulocytopoiesis is less efficient in neonates than in adults. Adult animals responded rapidly to lithium chloride treatment, showing a 134% increase in blood neutrophils on the second day of exposure and ultimately increasing by 260% by the tenth day. Newborn rats on the other hand, showed a 25% decrease in blood neutrophils after one day of treatment with lithium, then remained at that or at pretreatment levels throughout the subsequent 10 days. These observations suggest that hematopoietic tissue in the newborn is less responsive than is that of adults.

Indolent neutrophil response to endotoxin in newborn rats.

The blood neutrophil response to endotoxin challenge was determined in one-day-old and young adult rats to test the hypothesis that the neonate is unable to mobilize neutrophils from bone marrow to the peripheral circulation at a rate similar to adults. Adult animals responded to endotoxin with a brief neutropenia followed rapidly by marked neutrophilia. The maximum adult neutrophil count occurred at 11 hr after challenge and returned to baseline values by 28 hr. In contrast, one-day-old rats showed a prolonged neutropenia after a comparable injection. Peak neutrophil counts in neonates occurred later than those seen in adults (16 versus 11 hr) and were also lower. However, neutrophilia, once established in the neonates, persisted considerably longer than in adults. The age at which the adult response to endotoxin is achieved was assessed by bleeding animals of increasing ages 7 hr after endotoxin challenge. A gradual progression toward the adult neutrophil response began at 2 wk of age. The mose rapid change in endotoxin responsiveness occurred after 6 wk of age.