PULMONARY AND SYSTEMIC INFLAMMATORY RESPONSES IN RABBITS WITH GRAM-NEGATIVE PNEUMONIA

The major goals of this study were to define the relationships between intrapulmonary and systemic inflammatory responses in animals with gr am-negative pneumonia. We treated rabbits with intrapulmonary Escheric hia coli (1 x 10(7) to 1 x 10(10) du/ml), and then measured physiologi c, cellular, and molecular events in the lungs and systemic circulatio n for 24 h. The treatment protocols resulted in groups of animals that mimicked the stages of the septic inflammatory response in humans. An imals treated with low inocula had systemic changes consistent with sy stemic inflammatory response syndrome and cleared the bacteria and inf lammatory products from the lungs. Animals treated with high inocula f ailed to clear bacteria from the lungs, had severe intrapulmonary infl ammatory responses, and developed septic shock. Intrapulmonary leukocy te recruitment was directly related to the size of the bacterial inocu lum, but lung protein accumulation was not. Tumor neurosis factor-alph a (TNF-alpha), interleukin-8 (IL-8), and CRO were detectable in lung l avage fluid at 4 h and declined by 24 h in animals that cleared intrap ulmonary E. coli. In contrast, lavage TNF-alpha, IL-8, and GRO increas ed over 24 h in animals that failed to clear intrapulmonary bacteria. MCP-1 increased between 4 h and 24 h in the lungs of all of the animal s as the histologic response evolved from neutrophilic to mononuclear cell predominance. Thus, the intensity of systemic inflammatory and ph ysiologic responses to intrapulmonary gram-negative infection depends on the inoculum size and whether the bacteria are cleared from or prol iferate in the lungs. The results provide experimental support for the recently proposed classification of septic responses in humans.