Altered inflammatory responses in preterm children with cerebral palsy.

Abstract

Perinatal inflammatory responses contribute to periventricular leukomalacia (PVL) and cerebral palsy (CP) in preterm infants. Here, we examined whether preterm children with CP had altered inflammatory responses when school-aged. Thirty-two preterm children with PVL-induced CP (mean [+/-standard deviation] age, 7.2 +/- 3.6 years) and 32 control preterm children with normal neurodevelopment (6.2 +/- 2.2 years) and matched for gestational age were recruited. We measured tumor necrosis factor (TNF)-alpha levels in the plasma and the supernatants of peripheral blood mononuclear cells (PBMCs) before and after lipopolysaccharide (LPS) stimulation, and proinflammatory gene expression in the PBMCs. TNF-alpha expression was significantly higher in the plasma (p < 0.001) and supernatants of LPS-stimulated PBMCs (p = 0.003) in the CP group than in the control group. After LPS stimulation, the intracellular TNF-alpha level in the PBMCs was significantly lower in the control group (p = 0.016) and significantly higher in the CP group (p = 0.01). The CP group also had, in their nonstimulated PBMCs, significantly higher mRNA levels of inflammatory molecules: toll-like receptor 4 (TLR-4) (p = 0.0023), TNF-alpha (p = 0.0016), transforming growth factor-beta-activated kinase 1 (p = 0.038), IkappaB kinase-gamma (p = 0.029), and c-Jun N-terminal kinase (p = 0.045). The TLR-4 mRNA levels in the PBMCs were highly correlated with TNF-alpha levels in LPS-stimulated PBMCs (Spearman rank correlation = 0.38, p = 0.03). The finding that preterm children with PVL-induced CP have altered inflammatory responses indicates the possibility of programming effect of PVL or inflammation-related events during early life.