Progression of Peripheral Blood Mononuclear Cell Mitochondrial Function during the Early Phase of Sepsis in Intensive Care Unit Patients

Background Sepsis is a leading cause of ICU admission and is associated with high rates of multiorgan failure and mortality. Altered mitochondrial function is an essential component of the early sepsis syndrome. However, its progression over time in peripheral blood mononuclear cells (PBMCs), essential mediators of the initial inflammatory response, is thus far unclear. Our purpose was to investigate the progression of mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) in the early phase of sepsis in ICU patients. Methods A single-centre prospective observational cohort study was conducted in sepsis patients and compared with age- and sex-matched controls. We measured mitochondrial function using functional respirometry measurements (Oroboros O2K) in PBMCs thrice during the first week of ICU admission. RT-qPCR was used for semi-quantitative analysis of expression of genes involved in oxidative phosphorylation. Secondary endpoints included the associations between mitochondrial function and (I) sepsis severity and (II) clinical outcomes, including 3-month mortality. Results Basal, ATP-linked, maximal and proton leak associated respiration were increased in sepsis patients (n = 25) compared to matched controls (n = 24) at all time points. This was associated with increased expression of SDBH (complex II) and ATP5F1A (complex V). Increased basal respiration was associated with 3-month mortality (HR 3.794, 95%CI 1.018–14.149, p = 0.047). No differences were observed in other secondary outcomes. Conclusion PBMC mitochondria were shown to have an increased respiratory rate during the first week of sepsis, supported by increased expression of genes involved in oxidative phosphorylation. Moreover, a progressive increase in mitochondrial respiration was negatively associated with 3-month survival. These results suggest that the upregulation of basal respiration may serve as a proxy marker for sepsis severity and outcomes.