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Mitochondrial dysfunction in peripheral blood mononuclear cells in pediatric septic shock
Scott L Weiss1, Mary A Selak, Florin Tuluc
11Division of Critical Care Medicine, Department of Anesthesia and Critical Care, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 2Department of Emergency Medicine, Center for Resuscitation Science, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3Flow Cytometry Research Core, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA. 4Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 5Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Pediatric septic shock patients show mitochondrial dysfunction in immune cells, indicated by reduced energy reserves and uncoupling. This dysfunction, particularly mitochondrial membrane potential, correlates with the duration of organ injury.
Area of Science:
- Immunology
- Cellular Biology
- Pediatric Critical Care
Background:
- Mitochondrial dysfunction is linked to immune dysregulation and organ failure in adult sepsis.
- Pediatric data on mitochondrial function in sepsis are limited.
- Immune cells play a crucial role in the systemic response to sepsis.
Purpose of the Study:
- To investigate mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs) of pediatric septic shock patients.
- To determine the correlation between mitochondrial dysfunction in PBMCs and the severity of global organ injury.
- To assess changes in mitochondrial function over the course of septic illness.
Main Methods:
- Prospective observational study in an academic Pediatric Intensive Care Unit (PICU).
- Inclusion of 13 pediatric patients with septic shock and multiple organ failures, and 11 healthy controls.
- Ex vivo measurement of mitochondrial oxygen consumption and membrane potential (ΔΨm) in PBMCs on days 1-2 and 5-7 of illness.
Main Results:
- Septic PBMCs showed reduced spare respiratory capacity and increased mitochondrial uncoupling on days 1-2 compared to controls.
- These mitochondrial abnormalities normalized by days 5-7.
- Mitochondrial membrane potential (ΔΨm) showed a trend towards association with organ failure duration, with higher ΔΨm in patients recovering organ function.
Conclusions:
- Pediatric septic shock is characterized by mitochondrial dysfunction in PBMCs, including impaired bioenergetic reserve and uncoupling.
- Mitochondrial membrane potential, rather than respiration, appears associated with the duration of organ injury in pediatric sepsis.
- These findings highlight the role of mitochondrial health in pediatric sepsis outcomes.
