Correlation between increased levels of serum IL-18 and high frequency of neonatal brain damage

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To clarify the role of the high concentration of IL-18 to develop cerebral palsy in premature infants, we used mouse P19 embryonal carcinoma cells as a model for early neuronal differentiation. During differentiation of P19 cells, increased expression of IL-18mRNA transcribed from the first exon and IL-18 precursor protein was observed. However, exogenous mature IL-18 (active form) showed no effects on cell damage or neuronal differentiation. We then examined whether exogenous mature IL-18 influences human immature endothelial cells. cDNA microarray analysis showed that several genes were up- or down-regulated, suggesting that mature IL-18 may target immature endothelial cells, resulting in severe brain damages.