Acute and Persistent Alterations in Pulmonary Inflammatory Cells and Airway Mast Cells Induced by Sendai Virus Infection in Neonatal Rats

Abstract

Neonatal rats inoculated with parainfluenza type 1 (Sendai) virus develop alveolar dysplasia and bronchiolar hypoplasia by 30 to 110 days after inoculation. Weanling rats do not develop these abnormalities. Because neonatal animals have hyporesponsive immune and inflammatory cell functions, and because neonatal rats support pulmonary viral replication for longer duration and are delayed in their viral antibody response compared to weanling rats, we compared inflammatory and immune responses of two age groups of rats following viral inoculation. Data from quantitative bronchoalveolar lavage 1 to 29 days following viral inoculation demonstrated that neonates had significantly fewer ( P < 0.05) lymphocytes and macrophages in their bronchoalveolar fluid per cm2alveolar surface than weanlings. Magnitude of neutrophil responses in neonatal rats compared to weanlings were not depressed. Pulmonary interferon activity was lower in neonates than in weanlings at 2, 3, 4, and 5 days after viral inoculation. Neonates failed to make antibody following intraperitoneal inoculation of inactivated viral antigen, whereas weanling rats had detectable viral antibody by 3 to 5 days after injection of antigen. At 90 days after inoculation of neonates, viral-inoculated rats had over 100-fold greater numbers ( P < 0.05) of mast cells in enzyme-dissociated lung preparations compared to age-matched controls. Viral-inoculated rats had two- to three-fold greater densities of mast cells (#/mm) in bronchiolar walls ( P < 0.02) than did control rats. We conclude that the enhanced susceptibility of neonatal rats as compared to weanling rats to Sendai virus-induced abnormalities in alveolar and bronchiolar growth is associated with a less intense pulmonary lymphocytic inflammatory cell response as well as a less effective antibody and interferon response to viral infection. Neonatal viral infection also induces persistent increases in airway mast cells that might be important in the pathogenesis of viral-induced airway hyperreactivity.