| A Controlled Challenge Study on Di(2-ethylhexyl) Phthalate (DEHP) in House Dust and the Immune Response in Human Nasal Mucosa of Allergic Subjects Tom Deutschle,1 Rudolf Reiter,1 Werner Butte,2 Birger Heinzow,3 Tilman Keck,1 and Herbert Riechelmann4 1Department of Otorhinolaryngology, University of Ulm, Medical School, Ulm, Germany; 2Institute for Pure and Applied Chemistry, University of Oldenburg, Oldenburg, Germany; 3State Agency for Nature and Environment of Schleswig-Holstein, Department of Environmental Health and Toxicology, Flintbek, Germany; 4Department of Otorhinolaryngology, University Hospital, Medical University, Innsbruck, Austria Abstract 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 µg/m3 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: DEHPlow house dust increased eosinophil cationic protein, granulocyte-colony–stimulating factor (G-CSF) , interleukin (IL) -5, and IL-6, whereas DEHPhigh 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 DEHPhigh house dust compared with exposure to DEHPlow house dust, and fibroblast growth factor 9, IL-6, and transforming growth factor-β1, 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. Key words: allergy, cytokines, DEHP, di(2-ethylhexyl) phthalate, house dust, hypersensitivity, microarray analysis, nasal challenge, nasal exposure system, nasal mucosa. Environ Health Perspect 116:1487–1493 (2008) . doi:10.1289/ehp.11474 available via http://dx.doi.org/ [Online 7 July 2008] Address correspondence to T. Deutschle, Department of Otorhinolaryngology, University Hospital of Ulm, Frauensteige 14a, 89075 Ulm, Germany. Telephone: 49-731-500-59560. Fax: 49-31-00-6760. E-mail: tom.deutschle@uniklinik-ulm.de We thank K.C. Bergmann, Allergie- und Asthmaklinik, Bad-Lippspringe, Germany, for pollen identification, and M. Jerg, A. Rau, and B. Rothermel for technical assistance. This work was supported by grant BWW22010 from the State of Baden Württemberg, Germany. The authors declare they have no competing financial interests. Received 12 March 2008 ; accepted 3 July 2008. The full version of this article is available for free in HTML or PDF formats. |