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Proinflammatory cytokine-receptor interaction model improves the predictability of cerebral white matter injury in
W Thomas Bass1, E Stephen Buescher, Pamela S Hair
1Division of Neonatal Medicine, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA.
Insights
Cytokine-receptor interactions, not individual levels, predict white matter injury (WMI) in preterm infants. This finding offers new insights into inflammation
Area of Science:
- Neonatal Neurology
- Immunology
- Biochemistry
Background:
- Cerebral white matter injury (WMI) in preterm infants is a significant concern.
- Proinflammatory cytokines are implicated in WMI pathogenesis.
- Soluble receptors modulate cytokine activity, influencing their biological impact.
Purpose of the Study:
- To investigate the predictive value of cytokine-receptor interactions for WMI in preterm infants.
- To determine if modeling cytokine-receptor complexes improves WMI prediction compared to individual analytes.
Main Methods:
- Plasma samples from 100 preterm infants were analyzed for key proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6) and their soluble receptors (sTNF-RI, sTNF-RII, sIL-1RA, sIL-6R).
- Cranial ultrasound (US) assessed WMI.
- Statistical models (logistic regression, ROC curves) evaluated associations between analyte concentrations, cytokine-receptor interactions, and WMI.
Main Results:
- No significant association was found between individual cytokine or soluble receptor concentrations and WMI development.
- Modeling the interaction between cytokines and their soluble receptors significantly enhanced the predictability of WMI.
- This suggests a complex interplay rather than isolated effects.
Conclusions:
- Cytokine-receptor interactions are crucial for understanding inflammation's role in preterm WMI.
- Focusing on these interactions offers a more accurate approach to predicting WMI than measuring individual cytokine or receptor levels alone.
- This highlights a potential therapeutic target area.
Abstract:
Proinflammatory cytokines have been variably linked to development of cerebral white matter injury (WMI) in preterm infants. Because soluble receptors tightly control cytokine bioactivity, we modeled cytokine-receptor interaction as a predictor of WMI. Plasma from 100 preterm infants was assayed for cytokines (tumor necrosis factor alpha, interleukin (IL-1beta, IL-6) and their soluble receptors (sTNF-RI), sTNF-RII, sIL-1RA, and sIL-6R). Cranial ultrasound (US) results were correlated with cytokine and receptor concentrations individually and with cytokine-receptor interaction models (PROC LOGISTIC; SAS Software). Receiver operating characteristic curves were constructed to determine the predictability of WMI. Fifty-two infants with normal US exams were compared with 21 infants with evidence of WMI. There was no association between individual cytokine or receptor concentrations and the development of WMI. However, modeling cytokines with their soluble receptors significantly improved the predictability of WMI. We concluded that consideration of cytokine-receptor interaction may be more important than individual cytokine concentrations alone in determining the role of inflammation in the pathogenesis of WMI in preterm infants.
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