Inflammation fails to explain young—Old difference in hyperoxia lethality

Abstract

The inflammation that accompanies oxygen toxicity to the lung is believed to magnify the damage and to be a significant factor in determining the ultimate extent of lung injury. The mechanism proposed for the increased lung damage associated with inflammation is the release of reactive oxygen species by leukocytes (PMNs) and macrophages that are recruited to the damaged lung. In an earlier study, when 2-mo and 27-mo male Fischer 344 rats were exposed to >98% oxygen, a significant difference was found in survival. The old rats lived approximately two times as long as the young rats. This study explored the hypothesis that the age-related lethality difference was due to a faster onset and greater extent of inflammation in the lungs of young rats than old. Following 55 h of exposure to >98% oxygen, bronchopulmonary lavage demonstrated no differences in protein or in neutrophil or macrophage composition. In addition, there was no significant difference in whole lung myeloperoxidase activity between the two age groups. Blinded light microscopy interpretation of lung sections provided evidence that there was significantly more inflammation in the lungs of old rats compared to young. This was confirmed by quantitative morphology using electronmicroscopy. These data, taken collectively, imply that a greater inflammatory response was not responsible for the earlier death of the young rats compared to the old.