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Altered innate immunity in neonatal encephalopathy

Presented at the Neonatal Society 2018 Summer Meeting.

O’Dea M1,2,3,4,5, Strickland T1,2, Kelly L1,2,3, O’Leary JJ2,3, Molloy EJ1,2,3,4,5,6

1 Discipline of Paediatrics and Child Health, Trinity College Dublin
2 Trinity Translational Medicine Institute, St James Hospital
3 Coombe Women and Infant’s University Hospital
4 National Maternity Hospital, Dublin
5 National Children’s Hospital, Tallaght
6 Our Lady’s Children’s Hospital, Crumlin

Background: Neonatal Encephalopathy (NE) is a devastating clinical condition mediated in part by systemic inflammation. Evaluation of this process is key in understanding the inflammatory response and informing the development of predictive biomarkers and immunomodulatory adjunctive therapies to therapeutic hypothermia. Hypothesis: To evaluate innate immune responses at baseline and post-LPS stimulation in NE compared to healthy controls.

Methods: Inflammasome gene expression, serum cytokines and neutrophil surface markers were analysed in whole blood from NE (n=28) and control infants (n=16) via RT-PCR, ELISA and flow cytometry. Results were correlated with neuroimaging. Ethical Approval and Parental Consent were obtained. The Research was funded by the Health Research Board.

Results: NLRP3 and IL-1β gene expression was upregulated at baseline in NEs and augmented post-LPS (p<0.05). However, NE demonstrated lower IL-1β and higher IL-1ra cytokine release following LPS compared to controls – suggesting a reciprocal anti-inflammatory response. IFN-γ, IL-6, TNF- α were higher in controls while TNF- β and VEGF were significantly higher (p<0.05) in NE at baseline and post-LPS. Neutrophil cell-surface marker (CD11b/TLR4) expression was reduced in NE versus controls. Higher TNF-β in NE was associated with abnormal neuroimaging.

Conclusion: Inflammation is altered in NE compared to controls at baseline and in response to LPS. Selective inhibition of systemic inflammation may represent a therapeutic target in NE.

Corresponding author: tstrickl@tcd.ie 

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