A Controlled Challenge Study on Di(2-ethylhexyl) Phthalate (DEHP) in House Dust and the Immune Response in Human Nasal Mucosa of Allergic Subjects

BACKGROUND Few studies have yet addressed the effects of di(2-ethylhexyl) phthalate (DEHP) in house dust on human nasal mucosa. OBJECTIVES We investigated the effects of house dust containing DEHP on nasal mucosa of healthy and house dust mite (HDM)-allergic subjects in a short-term exposure setting. METHODS We challenged 16 healthy and 16 HDM-allergic subjects for 3 hr with house dust at a concentration of 300 microg/m(3) containing either low (0.41 mg/g) or high (2.09 mg/g) levels of DEHP. Exposure to filtered air served as control. After exposure, we measured proteins and performed a DNA microarray analysis. RESULTS Nasal exposure to house dust with low or high DEHP had no effect on symptom scores. Healthy subjects had almost no response to inhaled dust, but HDM-allergic subjects showed varied responses: DEHP(low) house dust increased eosinophil cationic protein, granulocyte-colony-stimulating factor (G-CSF), interleukin (IL)-5, and IL-6, whereas DEHP(high) house dust decreased G-CSF and IL-6. Furthermore, in healthy subjects, DEHP concentration resulted in 10 differentially expressed genes, whereas 16 genes were differentially expressed in HDM-allergic subjects, among them anti-Müllerian hormone, which was significantly up-regulated after exposure to DEHP(high) house dust compared with exposure to DEHP(low) house dust, and fibroblast growth factor 9, IL-6, and transforming growth factor-beta1, which were down-regulated. CONCLUSIONS Short-term exposure to house dust with high concentrations of DEHP has attenuating effects on human nasal immune response in HDM-allergic subjects, concerning both gene expression and cytokines.