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Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants
Christian Schultz1, Christina Rott, Petra Temming
1Department of Pediatrics, Medical University of Lübeck, Lübeck, Germany. ChrSchultz@aol.com
Insights
Neonates, including preterm infants, show a stronger inflammatory response than adults, producing more interleukin-6 (IL-6) and interleukin-8 (IL-8). This finding challenges the view of immature neonatal immunity and has implications for understanding infant diseases.
Area of Science:
- Neonatal immunology
- Cytokine biology
- Inflammatory response
Background:
- Sepsis complications in neonates are linked to proinflammatory cytokines.
- Elevated IL-6 and IL-8 predict adverse outcomes in preterm infants.
- Neonates are thought to have a reduced capacity for cytokine production.
Purpose of the Study:
- To investigate the inflammatory response in term and preterm infants at the single-cell level.
- To clarify the cytokine production capabilities of neonatal monocytes.
- To challenge the prevailing view of immature neonatal inflammatory responses.
Main Methods:
- Monocytes from healthy adults and neonates (term, preterm, and infected preterm) were stimulated with endotoxin.
- Flow cytometry was used to analyze single-cell cytokine production (IL-6, IL-8).
- Dexamethasone preincubation was used to assess modulation of the inflammatory response.
Main Results:
- Term and preterm infants exhibited a higher percentage of IL-6- and IL-8-positive cells than adults.
- Dexamethasone reduced cytokine-positive cells, but IL-8 remained elevated in preterm infants (>32 wk) compared to adults.
- Neonates demonstrate a well-developed and enhanced inflammatory response.
Conclusions:
- Neonatal inflammatory response is not immature but rather enhanced compared to adults.
- Elevated IL-6 and IL-8 levels in neonates may play a significant role in inflammatory neonatal diseases.
- Findings necessitate a re-evaluation of the pathophysiology of inflammatory-triggered neonatal conditions.
Abstract:
There is growing evidence that sepsis-related complications in neonates are crucially mediated by the action of proinflammatory cytokines. It has previously been demonstrated that elevated IL-6 and IL-8 levels can predict brain damage and chronic lung disease in preterm infants. However, it is the current view that neonates have a reduced capability to produce proinflammatory cytokines. To clarify this issue, we analyzed the inflammatory response in term and preterm infants directly at the single cell level by flow cytometry. Endotoxin challenge was performed under defined conditions on monocytes obtained from 50 healthy adults and 119 neonates, which consist of 45 term infants, 63 preterm infants (26.1-36.7 wk of gestational age), and 11 preterm infants with proven infection (24.6-29.9 wk). Our results challenge the existing view of an immature inflammatory response by demonstrating that term infants and preterm infants display a higher percentage of IL-6- and IL-8-positive cells than adults. After preincubation with dexamethasone the number of cytokine-positive cells decreased in all groups, but the number of IL-8-positive cells remained higher in term and preterm infants >32 wk compared with adults. These observations demonstrate not only a well-developed but also an enhanced inflammatory response in term and preterm infants. Under consideration of several detrimental effects of IL-6 and IL-8, our data may have major implications on the pathophysiology of inflammatory-triggered neonatal diseases.