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Updated: Feb 14, 2026
A Data-Driven Approach to Quantifying Immune States in Sepsis
Published on: February 7, 2025
Early Immune Function and Duration of Organ Dysfunction in Critically III Children with Sepsis
Jennifer A Muszynski1,2, Ryan Nofziger3, Melissa Moore-Clingenpeel1,4
11 Division of Critical Care Medicine and.
Insights
Early immune suppression in children with sepsis is linked to prolonged organ dysfunction. This study highlights immune suppression as a potential marker for guiding future sepsis therapies in pediatric patients.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Infectious diseases
Background:
- Late immune suppression is a known risk factor for mortality in pediatric sepsis.
- The impact of early immune suppression on sepsis outcomes in children is not well understood.
Purpose of the Study:
- To investigate the association between early innate and adaptive immune suppression and the duration of organ dysfunction in children with severe sepsis or septic shock.
Main Methods:
- Prospective observational study involving 102 children with sepsis and 35 healthy controls.
- Immune function assessed via ex vivo LPS-induced TNF-α and PHA-induced IFN-γ production.
- Organ dysfunction monitored using consensus criteria.
Main Results:
- Children with sepsis exhibited significantly lower TNF-α and IFN-γ production compared to controls.
- Early innate and adaptive immune suppression correlated with increased days of multiple organ dysfunction syndrome (MODS) and overall organ dysfunction.
- Early innate immune suppression independently predicted longer durations of MODS and organ dysfunction.
Conclusions:
- Children with severe sepsis or septic shock display early innate and adaptive immune suppression.
- This early immune suppression is associated with prolonged organ dysfunction.
- These findings suggest immune suppression markers could guide immunomodulatory therapy development in pediatric sepsis.
Rationale:
Late immune suppression is associated with nosocomial infection and mortality in adults and children with sepsis. Relationships between early immune suppression and outcomes in children with sepsis remain unclear.
Objectives:
Prospective observational study to test the hypothesis that early innate and adaptive immune suppression are associated with longer duration of organ dysfunction in children with severe sepsis or septic shock.
Methods:
Children younger than 18 years of age meeting consensus criteria for severe sepsis or septic shock were sampled within 48 hours of sepsis onset. Healthy control subjects were sampled once. Innate immune function was quantified by whole blood ex vivo LPS-induced TNF-α (tumor necrosis factor-α) production capacity. Adaptive immune function was quantified by ex vivo phytohemagglutinin-induced IFN-γ production capacity.
Measurements And Main Results:
One hundred two children with sepsis and 35 healthy children were enrolled. Compared with healthy children, children with sepsis demonstrated lower LPS-induced TNF-α production (P < 0.0001) and lower phytohemagglutinin-induced IFN-γ production (P < 0.0001). Among children with sepsis, early innate and adaptive immune suppression were associated with greater number of days with multiple organ dysfunction syndrome and greater number of days with any organ dysfunction. On multivariable analyses, early innate immune suppression remained independently associated with increased multiple organ dysfunction syndrome days (adjusted relative risk, 1.2; 95% confidence interval, 1.03-1.5) and organ dysfunction days (adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3).
Conclusions:
Critically ill children with severe sepsis or septic shock demonstrate early innate and adaptive immune suppression. Early innate and adaptive immune suppression are associated with longer durations of organ dysfunction and may be useful markers to help guide future investigations of immunomodulatory therapies in children with sepsis.
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