Prior oral exposure to environmental immunosuppressive chemicals methoxychlor, parathion, or piperonyl butoxide aggravates allergic airway inflammation in NC/Nga mice.

BACKGROUND: Immunosuppressive environmental chemicals may increase the potency of allergens and thereby play a role in the development of respiratory tract allergies, such as allergic rhinitis and asthma. OBJECTIVES: We investigated the association between environmental immunosuppressive chemicals and the allergic airway inflammation development. METHODS: We used a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. NC/Nga mice were exposed orally to pesticides parathion (an organophosphate compound) or methoxychlor (an organochlorine compound), or to an insecticide synergist piperonyl butoxide, prior to OVA intraperitoneal sensitization and inhalation challenge. We assessed serum IgE levels, B-cell counts, cytokine production, IgE production in hilar lymph nodes, eosinophil counts, chemokine levels in bronchoalveolar lavage fluid, and cytokine gene expression in the lung. RESULTS: Exposure to environmental immunosuppressive chemicals markedly increased serum IgE - IgE-positive B-cells, IgE and cytokines in lymph nodes - eosinophils and chemokines in BALF - IL-10a and IL-17 in the lung. CONCLUSIONS: Allergic airway inflammation can be aggravated by prior exposure to immunosuppressive environmental chemicals.

Role of regulatory T cells in the induction of atopic dermatitis by immunosuppressive chemicals.

Immunosuppressive environmental chemicals may exacerbate allergic diseases, including atopic dermatitis (AD). We examined the effects of the immunosuppressive environmental chemicals methoxychlor, parathion, piperonyl butoxide, dexamethasone, and cyclophosphamide on picryl-chloride-induced AD in NC/Nga mice. Mice were orally exposed (age, 5 weeks) to these chemicals; during their sensitization and challenge (age, 8-12 weeks) with picryl chloride, we measured ear thickness and scored skin dryness, erythema, edema, and wounding. After the challenge, we analyzed dermatitis severity and cytokine gene expression in the pinna, serum levels of IgE and IgG2a, T- and B-cell numbers and cytokine production in auricular lymph nodes, and counted splenic regulatory T cells. Exposure to environmental immunosuppressive chemicals markedly increased dermatitis severity and gene expression in the pinna; serum IgE and IgG2a levels; and numbers of helper T cells and IgE-positive B cells, production of Th1 and Th2 cytokines, and production of IgE in auricular lymph-node cells and markedly decreased the numbers of splenic regulatory T cells. Prior exposure to immunosuppressive environmental chemicals aggravates AD; a decrease in the numbers of regulatory T cells may influence this process.