title: Transforming growth factor-beta 1 inhibits synthesis of cytokines in endotoxin-stimulated human whole blood.
abstract: OBJECTIVE
  To determine the potency of transforming growth factor-beta (TGF-beta) for inhibiting proinflammatory cytokine synthesis in endotoxin-stimulated human whole blood.
  
  
  METHODS
  Endotoxin-stimulated whole blood from healthy volunteers as an ex vivo model of endotoxemia was incubated with different concentrations of TGF-beta 1. Cytokine levels in plasma with a bioassay (for tumor necrosis factor alpha) or an enzyme-linked immunosorbent assay (for interleukin [IL]-1 beta and IL-6), messenger RNA (mRNA) expression with northern blotting, and protein levels with Western blotting were determined.
  
  
  RESULTS
  High TGF-beta 1 concentrations (> 100 pg/mL) inhibited (P < .05) secretion of tumor necrosis factor alpha, IL-1 beta, and IL-6 into lipopolysaccharide-stimulated whole blood, while low concentrations (< 50 pg/mL) were ineffective. Moreover, TGF-beta 1 inhibited mRNA expression of tumor necrosis factor alpha and IL-6 in a dose-dependent manner. In contrast, neither IL-1 beta mRNA expression nor IL-1 beta protein synthesis were attenuated by TGF-beta 1.
  
  
  CONCLUSIONS
  Transforming growth factor-beta 1, with its downregulatory effect on the synthesis and release of proinflammatory cytokines by phagocytic cells, represents an inhibitor of endotoxin-induced inflammatory reactions.
authors.affiliation: Division of Trauma Surgery, University Hospital Zurich, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Karres
authors.forename: J P
authors.initials: JP
authors.lastname: Kremer
authors.forename: U
authors.initials: U
authors.lastname: Steckholzer
authors.forename: J S
authors.initials: JS
authors.lastname: Kenney
authors.forename: W
authors.initials: W
authors.lastname: Ertel
mesh_terms: D001769:Blood / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D004731:Endotoxins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta