INHALATION OF SWINE DUST INDUCES CYTOKINE RELEASE IN THE UPPER AND LOWER AIRWAYS

In healthy subjects, acute inhalation of swine dust causes an influx o f inflammatory cells into the airways and increased bronchial responsi veness, The exposure may also cause fever and generalized symptoms, It seems likely that proinflammatory cytokines are involved in the respo nse to inhaled swine dust. Nasal and bronchoalveolar lavage (BAL) were performed before, and 7 and 24 h after the start of 3 h exposure to s wine dust, during a period of work in a swine confinement building, in 22 healthy subjects, Lavage fluids were analysed with regard to the c ellular response and concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha), Each subject carried personal samplers for exposure measurements, Inhalable dust an d airborne endotoxin, 3-hydroxylated (2-OH) fatty acid and muramic aci d were measured. Bronchial responsiveness to methacholine was investig ated 1-2 weeks before and 7 h after the start of the exposure. Exposur e caused fever (>38 degrees C) in three subjects, and approximately 25 % of the subjects experienced symptoms, Bronchial responsiveness to me thacholine increased by 3.5 (1.6-4.8) doubling doses (median (25th-75t h percentile)), Following exposure, granulocytes increased more than 5 0 fold in BAL fluid and more than 40 fold in nasal lavage fluid, IL-1 alpha and IL-1 beta increased significantly in BAL fluid (p<0.05) and nasal lavage fluid (p<0.01), IL-6 increased 25 fold in BAL and 15 fold in nasal lavage fluid p<0.001), TNF-alpha was below detection limit ( 0.25 ng . L(-1)) in most subjects before exposure and increased follow ing exposure to 3.8 (2.4-5.7) and 1.3 (0.6-2.3) ng . L(-1) in BAL and nasal lavage fluid, respectively, (p<0.001), Total inhalable dust was 20.5 (14.6-30.0) mg . m(-3) and the concentrations of airborne endotox in, 3-OH fatty acid and muramic acid were 1.2 (0.8-1.4), 3.5 (2.2-4.5) and 0.9 (0.3-1.9) mu g . m(-3), respectively, There was a significant correlation between the IL-6 response in BAL fluid and exposure to du st endotoxin activity and 3-OH fatty acids (p<0.05), Otherwise, no sig nificant correlations were found between exposure and the cytokine res ponse. We conclude that exposure to swine dust causes an intense upper and lower airway inflammation, which involves the proinflammatory cyt okines interleukin-1, interleukin-6 and tumour necrosis factor-alpha.