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Innate immune function predicts the development of nosocomial infection in critically injured children
Jennifer A Muszynski1, Ryan Nofziger, Kristin Greathouse
1*Pediatric Critical Care Medicine, Department of Pediatrics, and †The Research Institute, Nationwide Children's Hospital, Columbus, Ohio; ‡Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio; §Department of Pathology, Nationwide Children's Hospital, Columbus, Ohio; and ║Pediatric Surgery, Nationwide Children's Hospital, Columbus, Ohio; ¶Department of Neurological Surgery, University of California, San Francisco, San Francisco, California; and **Division of Hematology, The Ohio State University College of Medicine, Columbus; ††Emergency Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio.
Insights
Critical injury in children suppresses innate immune function, increasing nosocomial infection risk. Lower tumor necrosis factor-alpha (TNF-α) production capacity after trauma predicts infection development in pediatric patients.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Trauma research
Background:
- Critical injury in adults is linked to reduced innate immunity and increased infection risk.
- This relationship between immune suppression and infection has not been established in critically injured children.
Purpose of the Study:
- To investigate if critically injured children exhibit reduced innate immune function.
- To determine if the degree of immune suppression predicts the development of nosocomial infections in this population.
Main Methods:
- A longitudinal, prospective study enrolled critically injured children (≤18 years) and outpatient controls.
- Blood samples were analyzed for plasma cytokine levels and ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-α) production capacity.
Main Results:
- Critically injured children who developed nosocomial infections had higher IL-6 and IL-10 levels and lower TNF-α production capacity.
- Reduced TNF-α response (<520 pg/mL) in the first week post-injury strongly predicted infection risk.
- In transfused children, older red blood cell storage age correlated with lower innate immune function.
Conclusions:
- Trauma-induced innate immune suppression is prevalent in critically injured children, elevating nosocomial infection risk.
- Factors like red blood cell transfusion may exacerbate immune suppression.
- Further research into therapies for pediatric trauma-induced immune suppression is warranted.
Background:
Critical injury has been associated with reduction in innate immune function in adults, with infection risk being related to degree of immune suppression. This relationship has not been reported in critically injured children.
Hypothesis:
Innate immune function will be reduced in critically injured children, and the degree of reduction will predict the subsequent development of nosocomial infection.
Methods:
Children (≤18 years old) were enrolled in this longitudinal, prospective, observational, single-center study after admission to the pediatric intensive care unit following critical injury, along with a cohort of outpatient controls. Serial blood sampling was performed to evaluate plasma cytokine levels and innate immune function as measured by ex vivo lipopolysaccharide-induced tumor necrosis factor α (TNF-α) production capacity.
Results:
Seventy-six critically injured children (and 21 outpatient controls) were enrolled. Sixteen critically injured subjects developed nosocomial infection. Those subjects had higher plasma interleukin 6 and interleukin 10 levels on posttrauma days 1-2 compared with those who recovered without infection and outpatient controls. Ex vivo lipopolysaccharide-induced TNF-α production capacity was lower on posttrauma days 1-2 (P = 0.006) and over the first week following injury (P = 0.04) in those who went on to develop infection. A TNF-α response of less than 520 pg/mL at any time in the first week after injury was highly associated with infection risk by univariate and multivariate analysis. Among transfused children, longer red blood cell storage age, not transfusion volume, was associated with lower innate immune function (P < 0.0001). Trauma-induced innate immune suppression was reversible ex vivo via coculture of whole blood with granulocyte-macrophage colony-stimulating factor.
Conclusions:
Trauma-induced innate immune suppression is common in critically injured children and is associated with increased risks for the development of nosocomial infection. Potential exacerbating factors, including red blood cell transfusion, and potential therapies for pediatric trauma-induced innate immune suppression are deserving of further study.
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