title: Reduction of IL-12 p40 production in activated monocytes after exposure to diesel exhaust particles.
abstract: BACKGROUND
  A reduction of IL-12 production by lung macrophages may partly explain the presumed adjuvant effect of diesel exhaust particles (DEP) in allergy and asthma. IL-12 stimulates T helper type 1 (Th1) lymphocytes, which inhibit Th2 cells via Th1-specific cytokines. The aim of this study was to investigate the influence of DEP on the production of IL-12 p40 in lipopolysaccharide (LPS)-activated monocytes.
  
  
  METHODS
  The human monocytic cell line Mono-Mac-6 was stimulated with LPS (200 ng/ml) and grown with DEP (0-200 microg/ml) for 0, 6 or 24 h. IL-12 p40 and the pro-inflammatory cytokine TNF were analysed in the cell supernatants by ELISA and a cell assay, respectively.
  
  
  RESULTS
  Levels of IL-12 p40 correlated inversely with the DEP exposure concentrations, whereas TNF increased in parallel to the DEP concentrations. At a DEP concentration of 200 microg/ml, the amount of IL-12 p40 was 35% of that observed without DEP. The corresponding TNF value was 230% of the control. Reduced viability, binding of cytokines to DEP or endotoxin in the DEP samples cannot fully explain the changes in the concentrations of these two cytokines.
  
  
  CONCLUSIONS
  DEP seem to inhibit the production of IL-12 p40 and stimulate that of TNF in activated monocytes. This may partly explain the presumed adjuvant effect of DEP in atopy; by altering the Th1/Th2 balance via down-regulation of IL-12, the Th2 response characteristic of allergy and asthma may be favoured.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. asbjorn.nilsen@medisin.ntnu.no
authors.forename: A M
authors.initials: AM
authors.lastname: Nilsen
authors.forename: R
authors.initials: R
authors.lastname: Hagemann
authors.forename: H
authors.initials: H
authors.lastname: Eikås
authors.forename: K
authors.initials: K
authors.lastname: Egeberg
authors.forename: T
authors.initials: T
authors.lastname: Nørkov
authors.forename: A
authors.initials: A
authors.lastname: Sundan
mesh_terms: D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology; D018664:Interleukin-12 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D010316:Particle Size; D021122:Protein Subunits / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D001335:Vehicle Emissions / Q000009:adverse effects*
chemical_list: D008070:Lipopolysaccharides; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D018664:Interleukin-12