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Correlation of plasma cytokine elevations with mortality rate in children with sepsis
J S Sullivan1, L Kilpatrick, A T Costarino
1Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine 19104.
Insights
Elevated plasma cytokine levels, including tumor necrosis factor and interleukin-6, indicate higher mortality risk in pediatric sepsis patients. These inflammatory markers may guide immunotherapeutic interventions for better outcomes.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Critical Care Medicine
Background:
- Cytokines are key mediators of the immune response during bacterial infections.
- Understanding cytokine roles in pediatric sepsis is crucial for predicting outcomes.
- Previous research suggests a link between inflammatory markers and sepsis severity.
Purpose of the Study:
- To investigate plasma cytokine levels in children with sepsis.
- To determine if cytokine levels correlate with illness severity and mortality.
- To explore the potential of cytokines as biomarkers for sepsis management.
Main Methods:
- Measured plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-1 (IL-1) in 21 pediatric sepsis patients.
- Collected samples at presentation and at 12, 24, and 48 hours post-presentation.
- Compared cytokine levels between survivors and nonsurvivors, and correlated them with the Pediatric Risk of Mortality (PRISM) score.
Main Results:
- Cytokine levels were significantly elevated in sepsis patients compared to controls.
- Nonsurvivors had markedly higher TNF and IL-6 levels than survivors (p < 0.001), independent of PRISM score.
- Elevated IL-6 (> 2 ng/ml) during the first 48 hours was strongly associated with mortality (p < 0.001).
- TNF and IL-6 elevations were sustained longer in nonsurvivors; IL-1 elevations were transient.
Conclusions:
- Elevated plasma TNF, IL-6, and IL-1 are characteristic of pediatric bacterial sepsis.
- Sustained high levels of TNF and IL-6 are strong predictors of mortality in pediatric sepsis.
- Cytokine profiling may help identify pediatric sepsis patients who could benefit from immunotherapeutic interventions.
Abstract:
Cytokines are thought to be important endogenous mediators of the host immune response to bacterial infection. We hypothesized that plasma levels of cytokines are elevated in children with sepsis and that the magnitude of elevation of these cytokines is correlated with severity of illness and mortality rate. We determined plasma levels of tumor necrosis factor, interleukin-6, and interleukin-1 in 21 children with sepsis. Plasma samples were collected at presentation and at 12, 24, and 48 hours thereafter. Cytokine levels were elevated in pediatric patients with bacterial sepsis during the first 48 hours after presentation; levels were undetectable in study control subjects. The tumor necrosis factor and interleukin-6 levels (p less than 0.001), as well as levels of interleukin-1 (p = 0.05), were significantly higher in nonsurvivors than in survivors and were independent of severity of illness (pediatric risk of mortality (PRISM) score) at presentation. Elevations of tumor necrosis factor and interleukin-6 were sustained for longer than 24 to 48 hours in nonsurvivors: II-1 concentrations were significantly increased only at time zero. Of 11 children with an interleukin-6 value greater than 2 ng/ml during the first 48 hours, 10 died; only one of 10 not reaching that level died (p less than 0.001). Cytokines were elevated as frequently with gram-positive as with gram-negative infections. We speculate that cytokine determinations may identify children who might benefit from immunotherapeutic interventions.