PMID- 20798552 OWN - NLM STAT- MEDLINE DCOM- 20110614 LR - 20161125 IS - 1661-7819 (Electronic) IS - 1661-7800 (Linking) VI - 99 IP - 2 DP - 2011 TI - Lipopolysaccharide-induced expression of Th1/Th2 cytokines in whole neonatal cord and adult blood: role of nuclear factor-kappa B and p38 MAPK. PG - 140-5 LID - 10.1159/000313967 [doi] AB - BACKGROUND: Sepsis continues to be a leading cause of morbidity and mortality in newborns. OBJECTIVE: As both nuclear factor-kappa B (NF-kappaB) 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-kappaB and p38 MAPK in whole neonatal cord and adult blood. METHODS: Th1/Th2 cytokine concentrations and phosphorylation of NF-kappaB and p38 MAPK were determined by flow-cytometric analysis. RESULTS: Tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-10 concentrations were significantly elevated in supernatants of neonatal and adult blood after LPS stimulation for 4 h. IFN-gamma, IL-4, and IL-2 showed no significant alterations. Furthermore, TNF-alpha 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-kappaB showed no difference. Following inhibition of p38 MAPK with the specific inhibitor SB-202190, levels of TNF-alpha and IL-6 significantly decreased in neonatal and adult blood, whereas pharmacological inhibition of NF-kappaB 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. CI - Copyright (c) 2010 S. Karger AG, Basel. FAU - Koch, Lutz AU - Koch L AD - Department of Neonatology, University of Heidelberg, Medical School, Heidelberg, Germany. lutz.koch@med.uni-heidelberg.de FAU - Fritzsching, Benedikt AU - Fritzsching B FAU - Frommhold, David AU - Frommhold D FAU - Poeschl, Johannes AU - Poeschl J LA - eng PT - Journal Article DEP - 20100827 PL - Switzerland TA - Neonatology JT - Neonatology JID - 101286577 RN - 0 (Cytokines) RN - 0 (Enzyme Inhibitors) RN - 0 (Imidazoles) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Pyridines) RN - 0 (SC 514) RN - 0 (Thiophenes) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - PVX798P8GI (4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole) SB - IM MH - Adult MH - Cytokines/*biosynthesis/blood MH - Enzyme Inhibitors/pharmacology MH - Fetal Blood/drug effects/enzymology/*immunology MH - Flow Cytometry MH - Humans MH - Imidazoles/pharmacology MH - Infant, Newborn MH - Lipopolysaccharides/*pharmacology MH - NF-kappa B/antagonists & inhibitors/biosynthesis/blood MH - Phosphorylation/drug effects MH - Pyridines/pharmacology MH - Signal Transduction MH - Th1 Cells/drug effects/enzymology/immunology/*metabolism MH - Th2 Cells/drug effects/enzymology/immunology/*metabolism MH - Thiophenes/pharmacology MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*biosynthesis/blood EDAT- 2010/08/28 06:00 MHDA- 2011/06/15 06:00 CRDT- 2010/08/28 06:00 PHST- 2010/01/22 00:00 [received] PHST- 2010/04/15 00:00 [accepted] PHST- 2010/08/28 06:00 [entrez] PHST- 2010/08/28 06:00 [pubmed] PHST- 2011/06/15 06:00 [medline] AID - 000313967 [pii] AID - 10.1159/000313967 [doi] PST - ppublish SO - Neonatology. 2011;99(2):140-5. doi: 10.1159/000313967. Epub 2010 Aug 27.