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BACKGROUND: 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.

OBJECTIVES: We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects.

METHODS: 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 (ALIAS; n = 1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 (TLR4), encoding the endotoxin receptor]-by-environment interaction in the endotoxin leukocyte relationship using regression models with an interaction term.

RESULTS: There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186X10(3)/mu L (95% CI: 0.070, 0.301X10(3)/mu L) 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 ALIAS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p = 0.15).

CONCLUSIONS: 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 cndotoxin exposure in diverse settings.