A single exposure to organic dust of non-naïve non-exposed volunteers induces long-lasting symptoms of endotoxin tolerance.
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.
Hoffmann
Hans Jurgen
HJ
Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Germany. hansjuergen.hoffmann@get2net.dk
Iversen
Martin
M
Sigsgaard
Torben
T
Omland
Oyvind
O
Takai
Hisamitsu
H
Bonefeld-Jørgensen
Eva
E
Seedorf
Jens
J
Dahl
Ronald
R
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
D004391:Dust; D004731:Endotoxins; D006684:HLA-DR Antigens; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha