Acute and Subacute Oral Exposure to Inorganic Arsenic Significantly Impacted the Pathology of a Mouse Model With Th2‐ and Th17‐, But Not Th1‐Dependent Allergy Development

Increased blood levels of inorganic arsenic compounds (iAs) are associated with the onset of allergic diseases. This study investigated the direct relationship between oral exposure to iAs and the onset of several allergic diseases. A mouse model of type 1, 2, and 17 helper T cell (Th1, Th2, and Th17) dependent allergies was generated in female BALB/c mice by topical treatment with 2,4-dinitrochlorobenzene, toluene-2,4-diisocyanate, and imiquimod. Several concentrations of iAs (0, 0.3, 1, 3, and 10 mg/kg) were administered orally for 3 or 4 days during each allergen challenge. Itch behavior and changes in skin thickness were monitored, the animals were euthanized, and inflammatory responses in the auricular lymph nodes and skin were analyzed. The influence of subacute oral exposure to iAs (0.3 and 3, and 24-52 days) on the development of chronic Th2 allergy was examined using mouse models of TDI-induced atopic dermatitis and Dermatophagoides farinae-induced asthma. Acute oral exposure to iAs significantly exacerbated Th2- and Th17-dependent allergies, whereas Th1-dependent allergic reactions were not significantly influenced. The influence of iAs exposure on Th2- and Th17-dependent allergy development was corroborated by subacute oral exposure to low concentrations of iAs in a chronic model of Th2 allergy. Symptoms and immune reactions were significantly increased following iAs exposure. Our findings imply that oral exposure to inorganic arsenic significantly affects the pathology of a mouse model of Th2- and Th17-dependent allergy development, but not a Th1-dependent allergy.