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Published on: October 13, 2017
Cytokine kinetic profiles in children with acute lower respiratory tract infection: a post hoc descriptive analysis
A Fuchs1, V Gotta1, M-L Decker1
1Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.
Insights
Cytokine profiles in children with lower respiratory tract infection (LRTI) decrease faster than PCT or CRP. Elevated cytokines indicate LRTI severity and may guide treatment decisions.
Area of Science:
- Pediatric infectious diseases
- Immunology
- Biomarker discovery
Background:
- Standard inflammatory markers and chest radiography are insufficient for differentiating bacterial from non-bacterial lower respiratory tract infections (LRTI) in children.
- Cytokine profiles show potential as biomarkers for LRTI, but their role in identifying etiology, disease severity, and guiding antibiotic use requires further definition.
Purpose of the Study:
- To determine cytokine kinetic profiles over five days in pediatric LRTI patients.
- To investigate the relationship between cytokine patterns and clinical/laboratory variables, including disease severity and antibiotic treatment.
Main Methods:
- Analysis of three consecutive cytokine measurements (days 1, 3, and 5) from a randomized controlled trial (ProPAED study) in 181 pediatric patients (1 month to 18 years) with febrile LRTI.
- Evaluation of cytokine concentration differences over time and associations with clinical and laboratory data.
Main Results:
- Serum concentrations of multiple cytokines (IFN-γ, IL-1ra, IL-6, IL-10, IP-10, TNF-α) peaked on day 1 and declined significantly by day 3.
- Procalcitonin (PCT) and C-reactive protein (CRP) showed a slower decrease, with most reduction occurring between days 3 and 5.
- Elevated IL-6 was linked to hospital admission, antibiotic use, and prolonged treatment; bacteraemic patients had higher IL-1ra and IL-6 levels on day 1.
Conclusions:
- Cytokine levels decrease more rapidly than PCT or CRP in pediatric LRTI, suggesting earlier dynamic changes.
- Both pro- and anti-inflammatory cytokines show potential as indicators of LRTI severity in children.
Objectives:
Standard inflammatory markers and chest radiography lack the ability to discriminate bacterial from non-bacterial lower respiratory tract infection (LRTI). Cytokine profiles may serve as biomarkers for LRTI, but their applicability to identify aetiology, severity of disease and need for antibiotic prescription in children remains poorly defined. Objectives were to determine the cytokine kinetic profiles over 5 days in paediatric patients with LRTI, to investigate the relationship between cytokine patterns, and clinical and laboratory variables.
Methods:
We included patients aged 1 month to 18 years, with febrile LRTI and three consecutive cytokines measurements on days 1, 3 and 5 of a randomized controlled trial (ProPAED study). We evaluated differences in cytokine concentrations between days and associations with clinical and laboratory variables.
Results:
A total of 181 patients (median age 4.1 years) were included; 72/181 (40%) received antibiotics. Serum concentrations of interferon (IFN)-γ, interleukin (IL)-1ra, IL-6, IL-10, IFN-γ-inducible protein (IP)-10 and tumor necrosis factor-α were elevated on day 1 and decreased subsequently, with the greatest decline between day 1 and 3 (by -8 to >-94%). Procalcitonin (PCT) and C-reactive protein (CRP) values showed a protracted decrease with the most prominent reduction in concentrations between days 3 and 5. Significantly elevated IL-6 concentrations were associated with hospital admission, antibiotic treatment, and prolonged antibiotic treatment. Bacteraemic LRTI patients had higher concentrations of IL-1ra (p <0.0055) and IL-6 (p <0.0055) on day 1.
Conclusions:
We observed an earlier decrease of elevated cytokines compared to PCT or CRP. Both pro- and anti-inflammatory cytokines may serve as markers for severity of LRTI.
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