EFFECTS OF AGING ON ANTI-BACTERIAL MECHANISMS IN EXPERIMENTAL PNEUMONIA

Abstract
Disease-free mature (6-8 mo. old) and senescent (24-26 mo. old) C57BL/6 mice were infected with Staphylococcus aureus and Klebsiella pneumoniae by peroral intratracheal inoculation. LD50 was identical for both groups of animals with Staphylococcus (LD50 = 1.2 .times. 109 colony-forming units (cfu) and Klebsiella (LD50 = 2.3 .times. 108 cfu). After challenges with high inocula of Staphyloccus (3 .times. 108 cfu) or Klebsiella (3 .times. 107 cfu), senescent mice more rapidly cleared viable organisms from the lungs than did the younger animals; 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 .times. 104 cfu Klebsiella. In contrast to high-inoculum infection in which > 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 36S-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; these changes do not predispose to lethal infection.