Ex vivo cytokine release reflects sensitivity to occupational endotoxin exposure
Ex vivo cytokine release reflects sensitivity to occupational endotoxin exposure
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DOI：
10.1183/09031936.00161908
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发表时间：
2009-10-01
影响因子：
24.3
通讯作者：
Wouters, I. M.
中科院分区：
文献类型：
--
作者：
Smit, L. A. M.;Heederik, D.;Wouters, I. M.
并不是每个暴露在内毒素下的人都会出现呼吸道症状，即使在非常高的暴露水平下也是如此。为探讨体外脂多糖(LPS)诱导的细胞因子释放是否可以预测个体对职业内毒素暴露的敏感性，对412名农业工人进行了脂多糖(LPS)刺激的全血培养上清液中肿瘤坏死因子(TNF)-α、白介素1-β(IL-1β)和白介素10(IL-10)的检测，并进行了肺功能测定和呼吸症状问卷调查。对于每个细胞因子，根据细胞因子浓度的中位数将人群分为低响应者和高响应者。内毒素暴露水平是基于249次个人暴露测量确定的。高IL-10反应者比低IL-10反应者有更高的呼吸道症状发生率(优势比在2.03到5.10之间；p<；0.05)。肿瘤坏死因子-α反应与症状呈正相关，但不显著，而IL-1β反应与症状无相关性。对于所有三种细胞因子，反应在中位数以上的受试者显示内毒素暴露与哮喘症状之间存在显著的剂量-反应关系，内毒素暴露与较低的用力呼气量之间存在显著的相关性(P<；0.05)。相比之下，暴露-反应关系较弱，对低应答者无统计学意义。体外对内毒素的炎症反应在很大程度上反映了个人是否容易受到高职业性内毒素暴露引起的不良呼吸影响。
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)-1 beta 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-1 beta 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.