Impaired peripheral mononuclear cell metabolism in patients at risk of developing sepsis: A cohort study

Purpose Dysregulated immune response is a key driver of disease progression in sepsis and known to be associated with impaired cellular metabolism. This association has been studied mostly in the late stage sepsis patients. Here, we investigate whether such impairment in cellular metabolism is present in uncomplicated infection patients who do not develop sepsis. Methods Forty sepsis (fulfilled Sepsis-3 criteria) and 27 uncomplicated infection patients were recruited from the emergency department along with 20 healthy volunteers. Whole blood was collected for measurement of gene expression, cytokine levels and cellular metabolic functions (including mitochondrial respiration, oxidative stress and apoptosis). Results Our analysis revealed the impairment of mitochondrial respiration in uncomplicated infection and sepsis patients (p value <0.05), with greater degree of impairment noted in the established sepsis. The impairment was significantly correlated with increased mitochondrial oxidative stress level; the latter was increased in uncomplicated infection and more so in established sepsis patients. Further analysis revealed that the oxidative stress level correlated significantly with cytokine level (tumor necrosis factor-α) and gene expression levels (CYCS, TP53, SLC24A24 and TSPO). Conclusions These findings suggest that impaired immune cell metabolism is present in infection patients without presenting sepsis, thereby opening potential window for early diagnosis and intervention (e.g. antioxidant therapy) in such patients.