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Altered Cytokine Endotoxin Responses in Neonatal Encephalopathy Predict MRI Outcomes.
Mary Isabel O'Dea1,2,3,4,5,6,7,8, Lynne A Kelly2,3,8, Ellen McKenna2,3
1National Maternity Hospital, Dublin, Ireland.
Frontiers in Pediatrics
|October 29, 2021
Summary
Neonatal encephalopathy (NE) involves altered cytokine profiles, with lipopolysaccharide (LPS) stimulation revealing more significant immune differences. These findings may improve predicting brain imaging abnormalities in NE infants.
Area of Science:
- Neonatal immunology
- Neuroinflammation
- Cytokine signaling
Background:
- Neonatal encephalopathy (NE) is a critical condition linked to poor neurodevelopmental outcomes and systemic inflammation.
- Cytokines, both pro-inflammatory and anti-inflammatory, are implicated in NE pathogenesis by modulating innate immune cells.
Purpose of the Study:
- To investigate differences in cytokine profiles between infants with NE and healthy controls.
- To assess the impact of lipopolysaccharide (LPS) stimulation on cytokine responses in NE.
- To explore the predictive value of cytokines for short-term neurodevelopmental outcomes, including MRI findings.
Main Methods:
- Eighty-seven infants (53 NE, 34 controls) were studied.
- Whole blood samples were analyzed using a 14-spot ELISA Multiplex Cytokine Array at baseline and after LPS stimulation.
- Cytokine levels were compared between groups, and associations with Sarnat stage, seizures, and MRI were examined.
Main Results:
- NE infants showed elevated baseline erythropoietin (Epo), IL-6, and IL-1ra, and reduced VEGF compared to controls.
- LPS stimulation revealed exaggerated Epo and IL-1ra responses in NE infants, alongside lower levels of other cytokines (IL-8, IL-2, IL-6, TNF-α, GM-CSF, VEGF, IFN-γ).
- Elevated GM-CSF, IFN-γ, IL-1β, IL-1ra, and VEGF were noted in NE infants with abnormal MRI; TNF-α predicted abnormal brain imaging both pre- and post-LPS stimulation.
Conclusions:
- Infants with NE exhibit distinct cytokine responses compared to controls, with LPS stimulation enhancing these differences.
- Cytokine analysis, particularly with LPS challenge, shows potential for predicting abnormal MRI findings in NE.
- Understanding these immune responses in NE infants undergoing therapeutic hypothermia may guide future immunomodulatory treatments.
