Short-Term Inflammatory Biomarker Profiles Are Associated With Deficient Mitochondrial Bioenergetics in Lymphocytes of Septic Shock Patients—a Prospective Cohort Study

Abstract

Introduction: A biomarker strategy based on the quantification of an immune profile could provide a clinical understanding of the inflammatory state in patients with sepsis and its potential implications for the bioenergetic state of lymphocytes, whose metabolism is associated with altered outcomes in sepsis. The objective of this study is to investigate the association between mitochondrial respiratory states and inflammatory biomarkers in patients with septic shock. Methods: This prospective cohort study included patients with septic shock. Routine, complex I, complex II respiration, and biochemical coupling efficiency were measured to evaluate mitochondrial activity. We measured IL-1ß, IL-6, IL-10, total lymphocyte count, and C-reactive protein levels on days 1 and 3 of septic shock management as well as mitochondrial variables. The variability of these measurements was evaluated using delta counts (days 3–1 counts). Results: Sixty-four patients were included in this analysis. There was a negative correlation between complex II respiration and IL-1ß (Spearman ρ, −0.275; P = 0.028). Biochemical coupling efficiency at day 1 was negative correlated with IL-6: Spearman ρ, −0.247; P = 0.05. Delta complex II respiration was negatively correlated with delta IL-6 (Spearman ρ, −0.261; P = 0.042). Delta complex I respiration was negatively correlated with delta IL-6 (Spearman ρ, −0.346; P = 0.006), and delta routine respiration was also negatively correlated with both delta IL-10 (Spearman ρ, −0.257; P = 0.046) and delta IL-6 (Spearman ρ, −0.32; P = 0.012). Conclusions: The metabolic change observed in mitochondrial complex I and complex II of lymphocytes is associated with a decrease in IL-6 levels, which can signal a decrease in global inflammatory activity.

Metabolic Reprogramming and Its Regulatory Mechanism in Sepsis-Mediated Inflammation

“…Wagner et al 94 investigated the association between mitochondrial respiratory states and inflammatory biomarkers in patients with septic shock, found that metabolic change observed in mitochondrial complex I and complex II of lymphocytes is associated with a decrease in IL-6 levels, which can signal a decrease in global inflammatory activity. Fatmi et al 95 have shown that miR-26a represents a promising biomarker for neonatal sepsis, and miR-23b can be used as a tool for predicting early and late neonatal sepsis progression and fatal outcomes.…”

Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury

“…Moreover, decreased mitochondrial function of mononuclear cells in critically ill patients is associated with increased mortality rates (Nedel et al, 2021). In critically ill patients, mitochondrial Complexes I and II functions were negatively correlated with increased pro-inflammatory cytokines IL-1β and IL-6 (Nedel et al, 2022). The mechanisms that support metabolic adaptations in microglia/macrophages are still under investigation.…”