title: TDI can induce respiratory allergy with Th2-dominated response in mice.
abstract: Toluene diisocyanate (TDI), a highly reactive industrial chemical is one of the leading causes of occupation-related asthma in industrialized countries. The pathophysiology of TDI-induced asthma, however, remains poorly understood, in part due to a lack of appropriate animal models. In this study, four models of TDI-sensitised mice were investigated. In model number 1, the mice were sensitised for 4 h/day on four consecutive days to 3 ppm inhaled TDI and challenged twice for 4 h each time with 0.3 ppm inhaled TDI. In model number 2, the sensitising condition was similar to that of model 1, but the challenge conditions involved an initial inhalation of 2 ppmTDI for 4h and then tracheal instillation with 50 microg/mouse albumin-TDI. In model number 3, the mice were sensitised first to 25% TDI (sc) and then three times for 4 h each time to 1 ppm inhaled TDI and challenged twice for 4h each time with 0.1 ppm inhalated TDI. In model number 4, the mice were first sensitised to 1% TDI by skin application and then with 0.2% TDI by tracheal instillation and challenged tree times by tracheal instillation of 0.1% TDI. In model number 4, skin application followed by tracheal instillations of TDI led to local and systemic Th2-dominated immune responses that were characterized: (1) in the lung-associated lymph nodes by a decrease in Th1 cytokine (IFN-gamma) production associated with an increase in Th2 cytokine (IL-4, IL-5, IL-3) production; (2) in the lungs by an allergic inflammation throughout the conducting airways: goblet cell proliferation and eosinophil influx and; (3) in the serums by increased total and specific IgE levels, 17.5- and 3.5-fold higher than that of the controls, respectively. The conditions used for sensitisation in the other models, i.e. inhalation or subcutaneous administration plus inhalation, failed to induce a strong Th2 response like that observed in model number 4. The findings indicate that TDI can induce a Th2-dominated response in mice when administered by topical application plus tracheal instillation for sensitisation and by intra-tracheal instillation for challenge (model number 4). This mouse Th2 model of TDI-induced airway allergy can, in several aspects, mimic occupational TDI asthma in humans and may prove to be useful in determining the mechanistic basis behind this disease.
authors.affiliation: Institut National de Recherche et de Sécurité, INRS, Avenue de Bourgogne, B.P. 27, 54501 Vandoeuvre Cedex, France. masarin.ban@inrs.fr
authors.forename: Masarin
authors.initials: M
authors.lastname: Ban
authors.forename: Georges
authors.initials: G
authors.lastname: Morel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Langonné
authors.forename: Nelly
authors.initials: N
authors.lastname: Huguet
authors.forename: Elsa
authors.initials: E
authors.lastname: Pépin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Binet
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D019570:Inhalation Exposure; D007279:Injections, Subcutaneous; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology*; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
chemical_list: D016207:Cytokines; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E