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Occurrence of marked sepsis-induced immunosuppression in pediatric septic shock: a pilot study
Solenn Remy1, Karine Kolev-Descamps1, Morgane Gossez2
1Hospices Civils de Lyon, Paediatric Intensive Care Unit, Mother and Children University Hospital, 59 Boulevard Pinel, 69500, Bron, France.
Insights
Pediatric septic shock alters immune function, with lower monocyte human leukocyte antigen-DR (mHLA-DR) expression linked to increased secondary infections. This suggests potential for immunostimulation to prevent nosocomial infections in critically ill children.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Infectious diseases
Background:
- Sepsis-induced immunosuppression is well-documented in adults but poorly understood in children.
- Pediatric septic shock requires further investigation into immune function alterations.
Purpose of the Study:
- To investigate immune functions, including innate and adaptive immunity, in children with septic shock.
- To assess associations between inflammatory response, immunosuppression, and secondary acquired infections in pediatric sepsis.
Main Methods:
- Prospective observational study of children (1 month–18 years) with septic shock.
- Immunomonitoring included monocyte human leukocyte antigen-DR (mHLA-DR) expression, lymphocyte subsets, and cytokine concentrations.
- Comparison with age-matched controls undergoing elective surgery.
Main Results:
- Pediatric septic shock patients exhibited lymphopenia and significantly lower mHLA-DR levels compared to controls.
- Elevated pro-inflammatory cytokines (IL-6, IL-8, TNF-α) were observed in the early phase of sepsis.
- Lower day 3-5 mHLA-DR and higher early pro-inflammatory cytokines were associated with secondary acquired infections.
Conclusions:
- Increased initial inflammatory cytokine production correlates with impaired innate immunity, indicated by low mHLA-DR expression.
- Decreased mHLA-DR expression in children with septic shock is linked to a higher incidence of secondary infections.
- Results support further multicenter studies to explore immunostimulation strategies for preventing nosocomial infections in pediatric intensive care units.
Background:
While the process of sepsis-induced immunosuppression is now well described in adults, very little information is available on immune functions in pediatric sepsis. The current study investigated this in children with septic shock by performing immunomonitoring, including both innate (monocyte human leukocyte antigen-DR, mHLA-DR, expression) and adaptive immunity (lymphocyte subsets count), as well as cytokine concentrations (IL-6, IL-8, IL-10, IL-1Ra, TNF-α, IFN-γ). Subsequent objectives were to assess the associations between inflammatory response, potential immunosuppression and secondary acquired infection occurrence.
Methods:
Single-center prospective observational study, including children aged between 1 month and 18 years admitted to pediatric intensive care unit (PICU) for septic shock. Age-matched controls were children hospitalized for elective surgery without any infectious criteria. Blood was sampled at day 1-2, 3-5, and 7-9 after sepsis onset. mHLA-DR and lymphocyte subsets count were measured by flow cytometry and cytokine concentrations by Luminex technology.
Results:
A total of 26 children and 30 controls were included. Patients had lymphopenia, and mHLA-DR levels were significantly lower than controls at each time point (p < 0.0001). All cytokines peaked at day 1-2. Children with secondary acquired infection had lower day 3-5 mHLA-DR and higher pro-inflammatory cytokine concentrations (IL-6, IL-8 and TNF-α) at day 1-2 compared to children without secondary acquired infection.
Conclusions:
The higher initial inflammatory cytokine production was, the more innate immunity was altered, while evaluated by low mHLA-DR expression. Children with decreased mHLA-DR expression developed more secondary acquired infections. Upon confirmation in multicenter cohorts, these results pave the way for immunostimulation for the most immunosuppressed children in order to prevent nosocomial infections in PICU. Trial registration PedIRIS study NCT02848144. Retrospectively registered 28 July 2016.
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