Lipopolysaccharide-Induced Expression of Th1/Th2 Cytokines in Whole Neonatal Cord and Adult Blood: Role of Nuclear Factor-Kappa B and p38 MAPK.
Summary of "Lipopolysaccharide-Induced Expression of Th1/Th2 Cytokines in Whole Neonatal Cord and Adult Blood: Role of Nuclear Factor-Kappa B and p38 MAPK."
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.
Affiliation
Department of Neonatology, University of Heidelberg, Medical School, Heidelberg, Germany.
Journal Details
This article was published in the following journal.
Name: Neonatology
ISSN: 1661-7819
Pages: 140-145
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20798552
- DOI: http://dx.doi.org/10.1159/000313967
Medical and Biotech [MESH] Definitions
Urea Cycle Disorders, Inborn
Rare congenital metabolism disorders of the urea cycle. The disorders are due to mutations that result in complete (neonatal onset) or partial (childhood or adult onset) inactivity of an enzyme, involved in the urea cycle. Neonatal onset results in clinical features that include irritability, vomiting, lethargy, seizures, NEONATAL HYPOTONIA; RESPIRATORY ALKALOSIS; HYPERAMMONEMIA; coma, and death. Survivors of the neonatal onset and childhood/adult onset disorders share common risks for ENCEPHALOPATHIES, METABOLIC, INBORN; and RESPIRATORY ALKALOSIS due to HYPERAMMONEMIA.
Hypothermia, Induced
Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries.
Jaundice, Neonatal
Yellow discoloration of the SKIN; MUCOUS MEMBRANE; and SCLERA in the NEWBORN. It is a sign of NEONATAL HYPERBILIRUBINEMIA. Most cases are transient self-limiting (PHYSIOLOGICAL NEONATAL JAUNDICE) occurring in the first week of life, but some can be a sign of pathological disorders, particularly LIVER DISEASES.
O Antigens
The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Hyperbilirubinemia, Neonatal
Accumulation of BILIRUBIN, a breakdown product of HEME PROTEINS, in the BLOOD during the first weeks of life. This may lead to NEONATAL JAUNDICE. The excess bilirubin may exist in the unconjugated (indirect) or the conjugated (direct) form. The condition may be self-limiting (PHYSIOLOGICAL NEONATAL JAUNDICE) or pathological with toxic levels of bilirubin.
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