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.

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.