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Effect of Age on Respiratory Defense Mechanisms^*

Pulmonary Bacterial Clearance in Fischer 344 Rats After Intratracheal Instillation of Listeria monocytogenes

^* From the Health Effects Laboratory Division (Drs. Antonini, Yang, Ma, and Weissman, Ms. Roberts, and Mr. Barger), National Institute for Occupational Safety and Health, Morgantown, WV; and the Department of Environmental Health (Dr. Clarke), Harvard School of Public Health, Boston, MA.

Correspondence to: James M. Antonini, PhD, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd, Morgantown, WV 26505; e-mail: jga6{at}cdc.gov

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 10³, 5 x 10⁴, or 5 x 10⁵ Listeria monocytogenes, and the effects on mortality, lung inflammation, pulmonary bacterial clearance, alveolar macrophage (AM) function, and T-lymphocyte characterization were determined.

Measurements and results: In noninfected control animals, the older rats had lower numbers of AMs on lavage and a lower percentage of total T, CD4+, and 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 more extensive than those observed in the younger rats. Interestingly, AM chemiluminescence was enhanced, while AM NO, a highly important antibacterial defense product, was abrogated in the aged rats as compared to the young rats.

Conclusions: This study demonstrated that advanced age is associated with alterations in lung defense mechanisms and increased susceptibility to pulmonary bacterial infection marked by elevated mortality, slowed pulmonary bacterial clearance, and altered AM function, specifically a decrease in NO production. These observations are indicative of reduced pulmonary defense function in an older population of rats.

Key Words: age • chemiluminescence • host defense • Listeria monocytogenes • macrophage • nitric oxide • pulmonary clearance

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