title: A single exposure to organic dust of non-naïve non-exposed volunteers induces long-lasting symptoms of endotoxin tolerance.
abstract: BACKGROUND
  Work with occupational levels of organic dust is associated with a chronic inflammatory response that must somehow be controlled. Endotoxin tolerance has previously been described in vitro and animal studies as a mechanism that modifies the threshold at which response occurs.
  
  
  OBJECTIVE
  We investigated the response of non-naïve, currently non-exposed persons to a single exposure of organic dust in a swine confinement building.
  
  
  METHODS
  We exposed 16 non-naïve persons in a swine confinement building with low-to-moderate representative levels of organic dust and characterized their acute immune response.
  
  
  RESULTS
  Under work-like 3-hour exposure conditions, non-naïve volunteers developed an inflammatory response documented by an increase in interleukin-6 (IL-6) in bronchoalveolar lavage (BAL) from 3.1 to 6.1 pg/ml and visual indices of bronchial inflammation. Similarly, serum IL-6 increased with a peak 3 h after exposure. Tumor necrosis factor (TNF)-alpha was not detected in BAL, and serum TNF-alpha was reduced from 3.7 pg/ml at baseline to less than 2 pg/ml within 3 h after exposure, and remained decreased until 2 weeks after exposure. This is a cardinal marker for immune suppression which was confirmed by other markers: reduction in HLA-DR expression on alveolar macrophages and CD14 expression on blood monocytes.
  
  
  CONCLUSIONS
  We report findings that suggest that long-lasting endotoxin tolerance and immune suppression may be induced by a brief exposure to organic dust concentrations in the medium-low range of occupational levels.
authors.affiliation: Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Germany. hansjuergen.hoffmann@get2net.dk
authors.forename: Hans Jurgen
authors.initials: HJ
authors.lastname: Hoffmann
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
authors.forename: Torben
authors.initials: T
authors.lastname: Sigsgaard
authors.forename: Oyvind
authors.initials: O
authors.lastname: Omland
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Takai
authors.forename: Eva
authors.initials: E
authors.lastname: Bonefeld-Jørgensen
authors.forename: Jens
authors.initials: J
authors.lastname: Seedorf
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
mesh_terms: D000328:Adult; D004391:Dust / Q000276:immunology*; D004731:Endotoxins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D016273:Occupational Exposure; D011014:Pneumonia / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D004391:Dust; D004731:Endotoxins; D006684:HLA-DR Antigens; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha