Effects of aging on antibacterial mechanisms in experimental pneumonia

Disease-free mature (6 to 8 months old) and senescent (24 to 26 months old) C57BL/6 mice were infected with Staphylococcus aureus and Klebsiella pneumoniae by peroral intratracheal inoculation. The lethal inoculum for 50% of animals (LD50) was identical for both groups of animals with Staphylococcus LD50 = 1.2 X 10(9) colony-forming units (cfu] and Klebsiella (LD50 = 2.3 X 10(8) cfu). After challenges with high inocula of Staphylococcus (3 X 10(8) cfu) or Klebsiella (3 X 10(7) cfu), senescent mice more rapidly cleared viable organisms from the lungs than did the younger animals, and the differences were statistically significant at 48 h. The enhanced pulmonary clearance demonstrated by the older mice was associated with the recruitment of greater numbers of neutrophils into the bronchoalveolar spaces. When challenged with lower inoculums, mature mice cleared viable bacteria more rapidly than did the senescent animals, although a significant difference was observed only at 24 h after infection with 3 X 10(4) cfu Klebsiella. In contrast to high-inoculum infection in which greater than 90% of cells present in bronchoalveolar spaces were neutrophils, the predominant cells after low inoculum challenges remained alveolar macrophages in all groups. Differences in pulmonary clearance of viable bacteria in young and old mice were not associated with significant discrepancies in the rates of physical removal of 35S-methionine-labeled bacteria. Thus, the normal aging process results in alterations in the manner in which the host responds to pulmonary challenge with common bacterial pathogens, but these changes do not predispose to lethal infection.