title: Effects of prior oral exposure to combinations of environmental immunosuppressive agents on ovalbumin allergen-induced allergic airway inflammation in Balb/c mice.
abstract: Abstract Humans are exposed daily to multiple environmental chemicals in the atmosphere, in food, and in commercial products. Therefore, hazard identification and risk management must account for exposure to chemical mixtures. The objective of the study reported here was to investigate the effects of combinations of three well-known environmental immunotoxic chemicals - methoxychlor (MXC), an organochlorine compound; parathion (PARA), an organophosphate compound; and piperonyl butoxide (PBO), an agricultural insecticide synergist - by using a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Four-week-old Balb/c mice were exposed orally to either one or two of the environmental immunotoxic chemicals for five consecutive days, prior to intraperitoneal sensitization with OVA and an inhalation challenge. We assessed IgE levels in serum, B-cell counts, and cytokine production in hilar lymph nodes, and differential cell counts and levels of related chemokines in bronchoalveolar lavage fluid (BALF). Mice treated with MXC + PARA or PBO + MXC showed marked increases in serum IgE, IgE-positive B-cells and cytokines in lymph nodes, and differential cell counts and related chemokines in BALF compared with mice that received the vehicle control or the corresponding individual test substances. These results suggest that simultaneous exposure to multiple environmental chemicals aggravates allergic airway inflammation more than exposure to individual chemicals. It is expected that the results of this study will help others in their evaluation of immunotoxic combinational effects when conducting assessments of the safety of environmental/occupational chemicals.
authors.affiliation: Toxicology Division, Institute of Environmental Toxicology , Ibaraki , Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.forename: Risako
authors.initials: R
authors.lastname: Nishino
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kosaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kurosawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueda
authors.forename: Takanori
authors.initials: T
authors.lastname: Harada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D004867:Equipment Design; D005260:Female; D005434:Flow Cytometry; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000633:toxicity*; D019570:Inhalation Exposure; D007274:Injections, Intraperitoneal; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology; D013997:Time Factors; D018675:Toxicity Tests / Q000295:instrumentation / Q000379:methods
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D007166:Immunosuppressive Agents; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Allergic airway inflammation; environmental chemicals; methoxychlor; parathion; piperonyl butoxide