Gene expression in the model system of neonatal brain damage with increased levels of serum IL-18

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We found that IL-18 in cord blood serves as a biochemical marker of brain damages followed by cerebral palsy in premature infants, and sepsis is another factor to induce neonatal brain damages. We examined the effects of IL-18 and endotoxin LPS, one of the toll-like receptor(TLR) ligands, to human immature endothelial cells. The cDNA microarray analysis showed that the expression of several chemokine and receptor genes and the endometrial bleeding associated factor gene, also known as Lefty-A, was induced by LPS. Lefty A was highly induced by IL-18 in one cell line but moderately in the other. We also used CD34-positive human hair follicle-derived stem cells that can differentiate to keratinocytes and neuronal cells. LPS induced the expression of Lefty A, IL8R and IL5RA, and IL-18 enhanced the expression of several chemokines. By treatment with other TLR ligands, the expression of the chomokine family and the ICAM genes were induced at a constant level, but the expression levels of IL-18 were variable among cell strains.Recently, several reports noted that DNA polymorphisms vary clinical manifestations of severe infection. Taken together, in premature infants, severe infection and high serum IL-18 may cause damages to immature cells probably through TLR-mediated signals, and DNA polymorphisms may play an important role to modify the sensitivity to the signals.