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Not everyone exposed to endotoxin develops respiratory symptoms, even at very high exposure levels. The aim was to investigate whether ex vivo lipopolysaccharide (LPS)-induced cytokine release may be predictive of individual sensitivity to occupational endotoxin exposure. In 412 agricultural workers, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 release was measured in supernatants from LPS-stimulated whole blood, lung function was measured, and respiratory symptoms were assessed by questionnaire. For each cytokine, the population was dichotomised into low and high responders according to median cytokine concentrations. Endotoxin exposure levels were determined based on 249 personal exposure measurements. High IL-10 responders had a higher prevalence of airway symptoms than low IL-10 responders (odds ratios between 2.03 and 5.10; p<0.05). TNF-alpha response was positively, but not significantly, associated with symptoms, whereas no relationship was found between IL-1beta response and symptoms. For all three cytokines, subjects with above-median responses showed significant positive dose-response relationships between endotoxin exposure and asthma symptoms, and significant associations between endotoxin exposure and a lower forced expiratory volume in 1 s (p<0.05). In contrast, exposure-response relationships were weak and statistically nonsignificant for low responders. The ex vivo inflammatory response to LPS reflects, to a large extent, whether individuals are susceptible to adverse respiratory effects induced by high occupational endotoxin exposure.

In healthy subjects, acute inhalation of swine dust causes an influx of inflammatory cells into the airways and increased bronchial responsiveness. The exposure may also cause fever and generalized symptoms. It seems likely that proinflammatory cytokines are involved in the response 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 swine dust, during a period of work in a swine confinement building, in 22 healthy subjects. Lavage fluids were analysed with regard to the cellular 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 and airborne endotoxin, 3-hydroxylated (2-OH) fatty acid and muramic acid were measured. Bronchial responsiveness to methacholine was investigated 1-2 weeks before and 7 h after the start of the exposure. Exposure caused fever (> 38 degrees C) in three subjects, and approximately 25% of the subjects experienced symptoms. Bronchial responsiveness to methacholine increased by 3.5 (1.6-4.8) doubling doses (median (25th-75th percentile)). Following exposure, granulocytes increased more than 50 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 following 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 endotoxin, 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) microgram.m-3, respectively. There was a significant correlation between the IL-6 response in BAL fluid and exposure to dust endotoxin activity and 3-OH fatty acids (p < 0.05). Otherwise, no significant correlations were found between exposure and the cytokine response. We conclude that exposure to swine dust causes an intense upper and lower airway inflammation, which involves the proinflammatory cytokines interleukin-1, interleukin-6 and tumour necrosis factor-alpha.