Ex vivo cytokine release reflects sensitivity to occupational endotoxin exposure.
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.
Institute for Risk Assessment Sciences, Division Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands. L.A.Smit@uu.nl
L A M
LA
Smit
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D
Heederik
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G
Doekes
E J M
EJ
Krop
G T
GT
Rijkers
I M
IM
Wouters
D000328:Adult; D000368:Aged; D000382:Agricultural Workers' Diseases / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016273:Occupational Exposure / Q000706:statistics & numerical data*; D011237:Predictive Value of Tests; D015995:Prevalence; D012130:Respiratory Hypersensitivity / Q000453:epidemiology* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; C508609:IL10 protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10