A Single Exposure to Organic Dust of Non-Naïve Non-Exposed Volunteers Induces Long-Lasting Symptoms of Endotoxin ToleranceHoffmann H.J. · Iversen M. · Sigsgaard T. · Omland Ø. · Takai H. · Bonefeld-Jørgensen E. · Seedorf J. · Dahl R.
a Department of Respiratory Diseases, Aarhus University Hospital, bDepartment of Occupational and Environmental Medicine, Institute of Public Health, Aarhus University, Aarhus, cDepartment of Agricultural Engineering, Research Center Bygholm, Danish Institute of Agricultural Sciences, Horsens, and dDepartment of Occupational Medicine, Aalborg-Århus University Hospital, Aalborg, Denmark; eInstitute for Animal Hygiene, Welfare and Behaviour of Farm Animals, University of Veterinary Medicine Hannover, Hannover, Germany
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)-α was not detected in BAL, and serum TNF-α 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. Conclusion: 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.
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