Fessler Michael B, Carnes Megan U, Salo Päivi M, Wilkerson Jesse, Cohn Richard D, King Debra, Hoppin Jane A, Sandler Dale P, Travlos Greg, London Stephanie, Thorne Peter, Zeldin Darryl
Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA
Epidemiology Branch, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA
Environ Health Perspect. 2017 May 31;125(5):057010. doi: 10.1289/EHP661.
The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood.
We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects.
The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 (), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term.
There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×10/μL (95% CI: 0.070, 0.301×10/μL) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the haplotype defined by rs4986790 and rs4986791 (interaction p=0.15).
This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings. https://doi.org/10.1289/EHP661.
外周血白细胞计数是炎症的生物标志物,与全因死亡率相关。尽管急性白细胞增多症的病因已得到充分描述,但白细胞数量的慢性环境决定因素却知之甚少。
我们研究了人体受试者室内灰尘内毒素浓度与外周血白细胞计数之间的关系。
在2005 - 2006年国家健康与营养检查调查(NHANES,n = 6254)和农业肺健康研究(ALHS,n = 1708)中,通过线性回归评估内毒素与白细胞的关系。在ALHS中,我们使用带有交互项的回归模型测试了基因[编码内毒素受体的Toll样受体4()]与环境在内毒素 - 白细胞关系中的相互作用。
在NHANES中,内毒素浓度与白细胞总数之间存在统计学上显著的正相关[内毒素每增加10倍,估计变化为0.186×10⁹/μL(95%CI:0.070,0.301×10⁹/μL);p = 0.004]。在单核细胞、淋巴细胞和中性粒细胞中也发现了类似的正相关。分层分析显示哮喘和慢性阻塞性肺疾病可能存在效应修饰。在ALHS中我们观察到了类似的关联。对于白细胞总数,在ALHS中有提示性证据表明,由rs4986790和rs4986791定义的单倍型的次要等位基因携带者状态存在基因与环境的相互作用(交互作用p = 0.15)。
据我们所知,这是在全国性调查中首次报道室内灰尘内毒素与白细胞计数之间的关联。该发现已在农业人群中得到重复验证。外周血白细胞计数可能受到不同环境中住宅内毒素暴露的影响。https://doi.org/10.1289/EHP661