Impaired pulmonary clearance of pneumococci in neonatal rats

Lung infections are a common cause of morbidity and mortality in neonates. To evaluate neonatal lung defenses against pneumococci, we challenged rats with aerosols of encapsulated pneumococci in an airborne infection apparatus. Whereas adult rats cleared greater than 95% of inhaled type 1 or type 25 pneumococci within 4 h, pneumococci proliferated in the lungs of newborn rats and reached 200-600% of the baseline value by 4 h and 1000-1700% by 24 h. As neonatal rats matured, their ability to clear inhaled pneumococci improved, but compared with adults some impairment in clearance was present until approximately 4 wk of age. Newborn rats had significantly fewer resident alveolar macrophages per g of lung tissue than did adults (p less than 0.001). Although the number of resident macrophages increased with time, a significant deficit in alveolar macrophages persisted for the first 3 wk of life (p less than 0.01). Aerosols of pneumococci caused an influx of granulocytes into the lungs of adult rats within 4 h, compared with 24 h for neonatal rats. Even at 24 h after pneumococcal challenge, newborn rats had significantly fewer granulocytes per g of lung tissue (p less than 0.05) than did adults, although 7-day-old rats had reached an adult level by this time. Significant (p less than 0.05) increases in granulocyte chemotactic activity were observed in lavage fluids of adult, but not newborn, rats after pneumococcal challenge. Thus, impaired clearance of pneumococcal aerosols by neonatal rats was associated with an age-dependent deficiency in numbers of resident alveolar macrophages and impaired generation of chemotactic activity and recruitment of granulocytes to the lung.