Abstract
BackgroundMitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients.MethodsWe enrolled 66 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between January 2019 and October 2019. Respiratory, hemodynamic and bedside echocardiographic parameters were recorded. Plasma mtDNA, procalcitonin, interleukin 6, and interleukin 8 levels were examined.ResultsPlasma mtDNA levels within 24 h after admission were significantly increased in the group of septic patients with ALI [5.01 (3.38–6.64) vs 4.13 (3.20–5.07) log copies/µL, p 0.0172]. mtDNA levels were independently associated with mortality (hazard ratio, 3.2052; 95% CI 1.1608–8.8500; p 0.0253) and ALI risk (odds ratio 2.7506; 95% CI 1.1647–6.4959; p 0.0210). Patients with high mtDNA levels had worse outcomes, and post hoc tests showed significant differences in 28-day survival rates. Increased mtDNA levels were seen in patients with abdominal infection.ConclusionsIncreased plasma mtDNA levels within 24 h after admission were significantly associated with ALI incidence and mortality in septic patients.
Highlights
Mitochondrial DNA is a critical activator of inflammation
Increased plasma Mitochondrial DNA (mtDNA) levels within 24 h after admission were significantly associated with acute lung injury (ALI) inci‐ dence and mortality in septic patients
The composition of pulmonary infection sources was accordant in patients with or without lung injury; bloodstream and abdominal infections seemed to be more common in patients with ALI
Summary
Mitochondrial DNA (mtDNA) is a critical activator of inflammation. Circulating mtDNA released causes lung injury in experimental models. We hypothesized that elevated plasma mtDNA levels are associated with acute lung injury (ALI) in septic patients. Mitochondrial DNA (mtDNA), as a potential damageassociated molecular pattern (DAMP), has attracted intense research in recent years since it may contribute to the mechanism by which mitochondria regulate innate immunity [1]. Circulating mtDNA is capable of triggering innate immunity through multiple mechanisms, such as activating the Toll-like receptor 9 (TLR-9)/NF-κB pathway or NALP3 inflammasome [4, 5]. Elevated levels of plasma mtDNA are associated with sepsis, trauma or postcardiac arrest [1, 6,7,8,9]. Intervention with mtDNA in an animal study induced systemic inflammatory response syndrome (SIRS) and pulmonary edema [4], and blockade of TLR9 improved the lung histopathological changes, wet/dry ratios and inflammatory factor concentrations [10]. mtDNA has been shown
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