Abstract
BACKGROUND: Occupational exposure to endotoxin has been associated with reduced lung cancer risk. The mechanisms underlying this association are unclear, though immunological alterations likely play a role. Farmers who perform certain tasks (eg, raising hogs) can be highly exposed to endotoxin. We, therefore, leveraged measurements of circulating immune markers from a prior investigation among male farmers in the Biomarkers of Exposure and Effect in Agriculture study to evaluate associations with newly developed estimates of endotoxin exposure. METHODS: Our investigation included 122 non-smoking farmers from Iowa, oversampling those raising hogs. Serum levels of 60 markers were measured using multiplex bead-based assays and ELISA. Based on an algorithm linking measurement-based task intensity estimates with self-reported task frequency, we estimated cumulative endotoxin exposure in the 30 days up to sample collection. We used multivariable linear regression to estimate geometric mean ratios of immune markers across exposure quartiles. RESULTS: Higher endotoxin exposure in the last 30 days was associated with increased levels of fibroblast growth factor-2, macrophage inflammatory protein-3 alpha/CCL20 and sIL-4R (P(trend)≤0.02) and decreased levels of macrophage-derived chemokine/CCL22 (P(trend)=0.02). We also identified novel associations with several additional markers; those with the highest (vs lowest) exposure to endotoxin had decreased levels of TARC/CCL17, sCD27 and IL-1B. CONCLUSIONS: Several circulating immune markers were associated with endotoxin levels in an exposure-response manner. Our findings are consistent with prior work on hog farming and suggest possible biological mechanisms through which endotoxin may confer a reduced risk of lung cancer.