The impact of lung infection on wound repair responses

Abstract

Abstract The incidence of pulmonary infection is elevated in patients with traumatic injury, and the severity of disease, morbidity, and mortality is positively correlated with the degree of trauma. While this clinical problem is well documented, its mechanistic basis is not well understood. Current models are designed to assess the effect of trauma on the development of pneumonia, but lack the ability to measure the subsequent effect of lung infection on wound repair. We have established a model that allows for the simultaneous assessment of wound healing and lung responses in mice with surgical wounds and Influenza A virus (IAV) infection. Mice are wounded by the subcutaneous implantation of sterile polyvinyl alcohol (PVA) sponges or by excision of tail skin and infected with IAV 24 hours later. PVA sponge implantation allows for the assessment of cellular and cytokine responses to injury, while excisional tail wounding allows for the measurement of rate of repair. Our data demonstrate that IAV infection results in delayed wound repair. Furthermore, the wounds of infected mice have lower repair cytokine concentrations and decreased cellularity, mediated in part by impaired trafficking of Ly6Chi monocytes. Wounded mice with IAV infection also have elevated concentrations of proinflammatory cytokines and chemokines in the serum and bronchoalveolar lavage fluid, suggesting an inflated systemic inflammatory response. Taken together, these data indicate that the presence of viral lung infection impairs the normal progression of wound repair. Future studies will determine whether this effect is specific to viral infection, or whether other lung injuries including pulmonary bacterial infection have a similar effect on wound repair responses.