Time course of the inflammatory and oxidative stress response to pulmonary infection in mice

The pathophysiological response to pulmonary infection includes a surge of proinflammatory cytokines and excessive production of nitric oxide (NO), but the time changes are not sufficiently defined. The current study was designed to assess the time course of proinflammatory cytokines and NO production in a murine model of pulmonary infection. The injury was induced by intranasal administration of live Pseudomonas aeruginosa (3.2 × 10 ⁷ colony-forming units) in C57BL/6 wild-type mice. The animals were euthanized at 3, 6, 9, 12, and 15 hours postinjury. Additional mice received sham injury (0 hours; control). Lung tissue and plasma samples were harvested at the respective time points. The injury induced an early increase in interleukin (IL)-1 β protein in lung tissue that persisted during the entire study period with a peak at the 9-hour time point. The increases in TNF-α and IL-6 proteins in lung tissue were less intense, but showed a peak about 9 hours postinjury. The plasma levels of IL-1 β and tumor necrosis factor (TNF)-α protein were not elevated during the experimental period, but only an increase in plasma levels of IL-6 plasma protein was detected. These findings compensate for the limitations of previous experiments with similar infection models and improve the understanding of pathophysiologic alterations in response to pulmonary infection. In addition, the identification of the time changes of the described pathogenetic factors may enhance the timing of innovate therapeutic approaches in future experiments.