Mitochondrial damage-associated molecular patterns exacerbate acute lung injury following burn

Abstract Acute lung injury (ALI) is an inflammatory condition that can occur following infection or trauma and is accompanied by a 40-50% risk of mortality. Burn patients suffer from ALI even without smoke inhalation, rendering them susceptible to life-threatening pneumonia. While models exist to simulate ALI following sepsis, a model is needed to study the mechanisms that drive ALI after trauma. We hypothesize that damage associated molecular patterns (DAMPs) enter circulation following trauma and induce ALI, characterized by cellular infiltration into the lung accompanied by systemic inflammation. Because our 20% total body surface area burn model induces systemic inflammation but not ALI, we administered fragmented mitochondria (MTD) i.v. following the burn. Compared with unburned, vehicle-treated control mice, cellular recovery from lung washes doubled 3h post burn+MTD (mean 2.5± SD 0.5E5 vs. 5.0±0.7E5, *p<0.005), and remained elevated at 24h (6.2±1.7E5*) and 48h (8.2±3.5E5, p<0.05). While serum IL-6 was undetectable in control mice, it was elevated at 3h (348±49 pg/mL*) and 24h (168±47*) following burn+MTD. Our data indicates that i.v. administration of MTD in conjunction with burn injury leads to cellular infiltration into the lung characteristic of ALI that is prolonged up to 48h. Burn with MTD treatment also affected systemic inflammation, evidenced by serum IL-6. Using this model we can investigate immunotherapeutic strategies to attenuate ALI in trauma patients.