Altered Inflammasome activation in Neonatal Encephalopathy persists in Childhood.

Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines IL-1β, IL-1ra and IL-18 are activated by the NOD-, LRR- and NLRP3 inflammasome, furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in pro-inflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex ELISA in neonates and children with NE in the absence or presence of LPS endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1β and ASC by PCR. Serum samples from 40 NE patients at day 1 and day 3 of the first week of life and in 37 patients at age 4 to 7 were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on day 1 and day 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 upregulated in the presence of LPS in NE neonates and NLRP3 gene expression remained upregulated 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.