title: Transcriptional control of cytokine release from monocytes of the newborn: effects of endogenous and exogenous interleukin-10 versus dexamethasone.
abstract: BACKGROUND
  Monocytes play an important role in the fetal and neonatal inflammatory response syndrome. They are also the precursors of alveolar macrophages, microglial and Kupffer cells. Monocytes have pro-inflammatory (PI) and anti-inflammatory (AI) functions. Interleukin (IL)-10 is a potent AI cytokine released by monocytes.
  
  
  OBJECTIVE
  We determined the effects of endogenous and exogenous IL-10 versus equimolar levels of dexamethasone (DEX) on PI and AI cytokine release, as well as transcription factor DNA-binding activity, in endotoxin (lipopolysaccharide, LPS)-stimulated monocytes of the newborn.
  
  
  METHODS
  Monocytes were isolated into culture media from cord blood. ELISAs, electrophoretic mobility shift assays and Western blots were employed.
  
  
  RESULTS
  LPS-stimulated monocyte release of PI cytokines, tumor necrosis factor-alpha (TNF-alpha), IL-1beta and IL-8, over 18 h was significantly augmented by addition of an IL-10 monoclonal antibody. Exogenous IL-10 at 10(-8)M inhibited PI cytokine release by 89-97%, while DEX at an equimolar level had no effect. DNA-binding activities of the PI transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1), and the AI transcription factor signal transducer and activator of transcription 3 (STAT3) were induced over 18 h. DEX at 10(-8)M had no effect on any transcription factor DNA binding, but exogenous IL-10 at 10(-8)M produced a 60% inhibition of AP-1 DNA binding and enhanced phosphorylation of nuclear STAT3 for 18 h.
  
  
  CONCLUSIONS
  At therapeutic levels of DEX, monocyte release of PI cytokine was insensitive to DEX in comparison to IL-10. IL-10 or its mechanism of action could lead to new therapy for inflammatory disorders in the perinatal period.
authors.affiliation: Division of Neonatal-Perinatal Medicine, Schneider Children's Hospital, New Hyde Park, NY 11040, USA.
authors.forename: Lina A
authors.initials: LA
authors.lastname: Chusid
authors.forename: Lucy
authors.initials: L
authors.lastname: Pereira-Argenziano
authors.forename: Veronika
authors.initials: V
authors.lastname: Miskolci
authors.forename: Ivana
authors.initials: I
authors.lastname: Vancurova
authors.forename: Dennis
authors.initials: D
authors.lastname: Davidson
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; C508609:IL10 protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003907:Dexamethasone