title: Lipopolysaccharide-induced expression of Th1/Th2 cytokines in whole neonatal cord and adult blood: role of nuclear factor-kappa B and p38 MAPK.
abstract: BACKGROUND
  Sepsis continues to be a leading cause of morbidity and mortality in newborns.
  
  
  OBJECTIVE
  As both nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) appear to be critical mediators in inflammatory response, we studied the effects of lipopolysaccharide (LPS) on expression and function of NF-κB and p38 MAPK in whole neonatal cord and adult blood.
  
  
  METHODS
  Th1/Th2 cytokine concentrations and phosphorylation of NF-κB and p38 MAPK were determined by flow-cytometric analysis.
  
  
  RESULTS
  Tumor necrosis factor-alpha (TNF-α), IL-6, and IL-10 concentrations were significantly elevated in supernatants of neonatal and adult blood after LPS stimulation for 4 h. IFN-γ, IL-4, and IL-2 showed no significant alterations. Furthermore, TNF-α concentrations were significantly higher in adult compared to neonatal blood after LPS stimulation. Stimulation with LPS resulted in significantly decreased activation of p38 MAPK in neonatal blood, whereas NF-κB showed no difference. Following inhibition of p38 MAPK with the specific inhibitor SB-202190, levels of TNF-α and IL-6 significantly decreased in neonatal and adult blood, whereas pharmacological inhibition of NF-κB with SC-514 showed no significant effect on cytokine expression.
  
  
  CONCLUSIONS
  We conclude that p38 MAPK phosphorylation is crucially involved in LPS activation and could explain the differences in early cytokine response between neonatal and adult blood.
authors.affiliation: Department of Neonatology, University of Heidelberg, Medical School, Heidelberg, Germany. lutz.koch@med.uni-heidelberg.de
authors.forename: Lutz
authors.initials: L
authors.lastname: Koch
authors.forename: Benedikt
authors.initials: B
authors.lastname: Fritzsching
authors.forename: David
authors.initials: D
authors.lastname: Frommhold
authors.forename: Johannes
authors.initials: J
authors.lastname: Poeschl
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005312:Fetal Blood / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007231:Infant, Newborn; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D018417:Th1 Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011725:Pyridines; C477523:SC 514; D013876:Thiophenes; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole