title: Altered inflammatory responses in preterm children with cerebral palsy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Lin
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Chang
authors.forename: Shan-Tair
authors.initials: ST
authors.lastname: Wang
authors.forename: Ting-Yang
authors.initials: TY
authors.lastname: Lee
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
mesh_terms: D000328:Adult; D002547:Cerebral Palsy / Q000097:blood / Q000276:immunology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha