Effect of age on respiratory defense mechanisms - Pulmonary bacterial clearance in fischer 344 rats after intratracheal instillation of Listeria monocytogenes

Study objectives: To examine the lung defense mechanisms of both young and aged rats before and after pulmonary challenge with a bacterial pathogen. Design: Male Fischer 344 rats, either 2.5 months or 20 months of age, were intratracheally inoculated with 5 x 10(3), 5 X 10(4), or 5 X 10(5) Listeria monocytogenes, and the effects all mortality, lung inflammation, pulmonary bacterial clearance, alveolar macrophage (AM) Function, and T-lymphocyte c haracterization were determined. Measurements and results: In noninfected control animals, the older rats ha d lower numbers of AMs on lavage and a lower percentage of total T, CD4+, a nd CD8+ cells. No difference was observed between noninfected young and old rats in AM function, assessing both chemiluminescence and nitric oxide (NO ) production. After bacterial challenge, aged rats exhibited an increase in mortality, pulmonary infection, and edema, and lung lesions, which were mo re extensive than those observed in the younger rats. Interestingly, AM che miluminescence was enhanced, while AM NO, a highly important antibacterial defense product, was abrogated in the aged rats as compared to the young ra ts. Conclusions: This study demonstrated that advanced age is associated with a lterations in lung defense mechanisms and increased susceptibility to pulmo nary bacterial infection marked by elevated mortality, slowed pulmonary bac terial clearance, and altered AM function, specifically a decrease in NO pr oduction. These observations are indicative of reduced pulmonary defense fu nction in an older population of rats.