{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:12:05Z","timestamp":1785499925028,"version":"3.56.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":219,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NCH, Tallaght Hospital"},{"DOI":"10.13039\/100014364","name":"National Children's Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,17]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1\u03b2, 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-1\u03b2 and ASC by polymerase chain reaction (PCR). Serum samples from 40\u00a0NE patients at days\u00a01 and 3 of the first week of life and in 37\u00a0patients at age 4\u20137\u00a0years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days\u00a01 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-1\u03b2 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.<\/jats:p>","DOI":"10.1111\/cei.13598","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T08:00:41Z","timestamp":1616745641000},"page":"89-97","source":"Crossref","is-referenced-by-count":18,"title":["Altered inflammasome activation in neonatal encephalopathy persists in childhood"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-1143","authenticated-orcid":false,"given":"L A","family":"Kelly","sequence":"first","affiliation":[{"name":"Discipline of Paediatrics, Trinity College, University of Dublin, Dublin, Ireland"},{"name":"Trinity Translational Medicine Institute (TTMI), Trinity College Dublin and Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M I","family":"O'Dea","sequence":"additional","affiliation":[{"name":"Discipline of Paediatrics, Trinity College, University of Dublin, Dublin, Ireland"},{"name":"Trinity Translational Medicine Institute (TTMI), Trinity College Dublin and Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Zareen","sequence":"additional","affiliation":[{"name":"Discipline of Paediatrics, Trinity College, University of Dublin, Dublin, Ireland"},{"name":"Trinity Translational Medicine Institute (TTMI), Trinity College Dublin and Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland"},{"name":"Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Melo","sequence":"additional","affiliation":[{"name":"Discipline of Paediatrics, Trinity College, University of Dublin, Dublin, Ireland"},{"name":"Trinity Translational Medicine 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Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Sweetman","sequence":"additional","affiliation":[{"name":"National Maternity Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Butler","sequence":"additional","affiliation":[{"name":"Meso-Scale Diagnostics, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Vavasseur","sequence":"additional","affiliation":[{"name":"National Maternity Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Miletin","sequence":"additional","affiliation":[{"name":"Neonatology, Coombe Women and Infants University Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A F","family":"El-Khuffash","sequence":"additional","affiliation":[{"name":"The Rotunda Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L A J","family":"O'Neill","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J","family":"O'Leary","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E J","family":"Molloy","sequence":"additional","affiliation":[{"name":"Discipline of Paediatrics, Trinity College, University of Dublin, Dublin, Ireland"},{"name":"Trinity Translational Medicine Institute (TTMI), Trinity College Dublin and Trinity Research in Childhood Centre (TRiCC), Dublin, Ireland"},{"name":"Children's Hospital Ireland (CHI) at Tallaght, Dublin, Ireland"},{"name":"Neonatology, Coombe Women and Infants University Hospital, Dublin, Ireland"},{"name":"CHI at Crumlin, Dublin, 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