Pulmonary contusion is associated with toll-like receptor 4 upregulation and decreased susceptibility to pseudomonas pneumonia in a mouse model.

Pulmonary contusion is a major cause of respiratory failure in trauma patients. This injury frequently leads to immune suppression and infectious complications such as pneumonia. The mechanism whereby trauma leads to an immune suppressed state is poorly understood. To further study this phenomenon, we developed an animal model of pulmonary contusion complicated by pneumonia and assessed the effect of pulmonary contusion and pneumonia on toll-like receptor expression in alveolar macrophages. Using a mouse model, pulmonary contusion (PC) was induced on the right lung and pneumonia was induced with Pseudomonas aeruginosa (Pa) injected intratracheally 48 hours after injury. Susceptibility to pneumonia was assessed by mortality at seven days. Uninjured animals were used as controls. Bronchoalveolar lavage (BAL) fluid and blood were assayed 48 hours after injury and 24 hours after Pa instillation to look at markers of systemic inflammation. Toll-like receptor (TLR) expression in the initial inflammatory response was analyzed by flow cytometry. Unexpectedly, injured animals subjected to intratracheal injection of Pa at 48h after pulmonary contusion demonstrated increased survival compared to uninjured animals. BAL cytokine expression was increased significantly after Pa administration but not after PC alone. TLR4 expression on alveolar macrophages was significantly elevated in the injured group compared to sham but not in neutrophils. Animals subjected to PC are more resistant to mortality from infection with Pa and display an enhanced cytokine response when subsequently subjected to Pa. Increased expression of TLR4 on alveolar macrophages and enhanced innate immunity is a possible mechanism of increased cytokine production and decreased susceptibility to pneumonia.