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This Article Full Text Full Text (PDF) All Versions of this Article: 34/4/795    most recent 09031936.00161908v1 Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Smit, L. A. M. Articles by Wouters, I. M. PubMed PubMed Citation Articles by Smit, L. A. M. Articles by Wouters, I. M.

Ex vivo cytokine release reflects sensitivity to occupational endotoxin exposure

¹ Institute for Risk Assessment Sciences, Division Environmental Epidemiology, Utrecht University, ² Dept of Paediatrics, University Medical Center Utrecht, Utrecht, and ³ St Antonius Hospital, Dept of Medical Microbiology and Immunology, Nieuwegein, The Netherlands.

CORRESPONDENCE: L. A. M. Smit, Institute for Risk Assessment Sciences, Division Environmental Epidemiology, P.O. Box 80178, 3508 TD Utrecht, The Netherlands. E-mail: L.A.Smit{at}uu.nl

Keywords: Asthma, epidemiology, farming, lung function, occupational exposure, whole blood assay

Received: October 27, 2008
Accepted March 30, 2009

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)-, interleukin (IL)-1β 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- response was positively, but not significantly, associated with symptoms, whereas no relationship was found between IL-1β 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.