Altered inflammasome activation in neonatal encephalopathy persists in childhood.
Authors
Kelly, L AO'Dea, M I
Zareen, Z
Melo, A M
McKenna, E
Strickland, T
McEneaney, V
Donoghue, V
Boylan, G
Sweetman, D
Butler, J
Vavasseur, C
Miletin, J
El-Khuffash, A F
O'Neill, L A J
O'Leary, J J
Molloy, E J
Issue Date
2021-05-02Keywords
hypoxic-ischaemic encephalopathyinflammasome
inflammation
NEONATAL ENCEPHALOPATHY
CHILD HEALTH
Metadata
Show full item recordJournal
Clinical and experimental immunologyDOI
10.1111/cei.13598PubMed ID
33768526Abstract
Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1β, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1β and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1β gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention.Item Type
ArticleOther
Language
enEISSN
1365-2249ae974a485f413a2113503eed53cd6c53
10.1111/cei.13598
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