In this paper, Choi and colleagues analyzed levels of mitochondrial DNA in two prospective observational cohort studies and found that increased mtDNA levels are associated with ICU mortality, and improve risk prediction in medical ICU patients. The data suggests that mtDNA could serve as a viable plasma biomarker in MICU patients.

Introduction Sepsis produces a major socio-economic burden with significant morbidity and mortality. Recently described chemical mediators, termed specialized pro-resolving mediators, actively regulate the resolution of acute-inflammation. Design Herein, de-identified plasma was collected from sepsis patients (n=22 subjects) within 48h of admission to the Intensive Care Unit (ICU) and on days 3 and 7 thereafter and subjected to lipid mediator (LM) profiling. Measurements In all patients, we identified > 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene (LT)B4 and prostaglandin (PG)E2 and pro-resolving mediators resolvin (Rv) D1, RvD2, and protectin (PD)1. Main Results In sepsis non-survivors we found significantly higher inflammation-initiating mediators including PGF2α and LTB4 and pro-resolving mediators including RvE1, RvD5 and 17R-PD1 than was observed in surviving sepsis subjects. This signature was present at ICU admission and persisted for 7 days. Further analysis revealed increased respiratory failure in non-survivors. Higher inflammation-initiating mediators (including PGF2α) and select pro-resolving pathways were associated with the development of ARDS, while other traditional clinical indices were not predictive of ARDS development. Conclusions These results provide peripheral blood lipid mediator profiles in sepsis that correlate with survival and ARDS development, thus suggesting plausible novel biomarkers and biologic targets for critical illness.

SUMMARY The magnitude and duration of acute inflammation are controlled by active resolution programs involving specialized proresolving mediators (SPMs; resolvins and maresins) and microRNAs (miRNAs). Here, we report that miR-466l was temporally regulated in murine exudate-infiltrating leukocytes. Neutrophil miR-466l overexpression in vivo promoted initiation of inflammation that anteceded macrophage expression of this miRNA, which accelerated resolution when overexpressed. In macrophages, miR-466l overexpression increased prostanoids and SPMs (e.g., resolvin D1 [RvD1] and RvD5), which enhanced resolution. RvD1, RvD2, maresin 1 (MaR1), and apoptotic neutrophils reduced miR-466l expression within human macrophages, a feedback regulation that most likely prepares for homeostasis. miR-466l was upregulated in peripheral blood of sepsis patients, and its increase correlated with nonsurvival from sepsis. SPMs and miR-466l regulated transcription factors activator protein 1 and nuclear factor κB1 in miRNA biogenesis. These results demonstrate pivotal roles for SPMs and miR-466l in dynamic leukocyte plasticity during resolution of acute inflammatory responses.