title: Toluene diisocyanate and methylene diphenyl diisocyanate: asthmatic response and cross-reactivity in a mouse model.
abstract: Both 2,4-toluene diisocyanate (TDI) and 4,4-methylene diphenyl diisocyanate (MDI) can cause occupational asthma. In this study, we optimized our mouse model of chemical-induced asthma in the C57Bl/6 mice strain using the model agent TDI. Furthermore, we validated MDI in this mouse model and investigated whether cross-reactivity between TDI and MDI is present. On days 1 and 8, C57Bl/6 mice were dermally treated (20 µl/ear) with 3 % MDI, 2 % TDI or the vehicle acetone olive oil (AOO) (3:2). On day 15, they received a single oropharyngeal challenge with 0.04 % MDI, 0.01 % TDI or the vehicle AOO (4:1). One day later, airway hyperreactivity (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL) were assessed. Furthermore, total serum IgE levels, lymphocyte subpopulations in auricular lymph nodes and cytokine levels in supernatants of lymphocytes were measured. Both dermal sensitization with TDI or MDI resulted in increased total serum IgE levels along with T and B cell proliferation in the auricular lymph nodes. The auricular lymphocytes showed an increased release of both Th2 and Th1 cytokines. Mice sensitized and challenged with either TDI or MDI showed AHR, along with a predominant neutrophil lung inflammation. Mice sensitized with MDI and challenged with TDI or the other way around showed no AHR, nor BAL inflammation. Both TDI and MDI are able to induce an asthma-like response in this mouse model. However, cross-reactivity between both diisocyanates remained absent.
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49 mailbox 706, 3000, Leuven, Belgium.
authors.forename: Lore
authors.initials: L
authors.lastname: Pollaris
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49 mailbox 706, 3000, Leuven, Belgium.
authors.forename: Fien
authors.initials: F
authors.lastname: Devos
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49 mailbox 706, 3000, Leuven, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: De Vooght
authors.affiliation: Laboratory of Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, 3000, Leuven, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Seys
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49 mailbox 706, 3000, Leuven, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49 mailbox 706, 3000, Leuven, Belgium.
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
authors.affiliation: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49 mailbox 706, 3000, Leuven, Belgium. jeroen.vanoirbeek@kuleuven.be.
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Vanoirbeek
mesh_terms: D000395:Air Pollutants, Occupational / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D001249:Asthma / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D003429:Cross Reactions / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D017953:Isocyanates / Q000276:immunology / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D058408:Th1-Th2 Balance / Q000187:drug effects; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology / Q000633:toxicity*; D001559:Benzhydryl Compounds
chemical_list: D000395:Air Pollutants, Occupational; D007073:Immunoglobulin E; D017953:Isocyanates; D014051:Toluene 2,4-Diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds
keywords: 2,4-Toluene diisocyanate; 4,4′-Methylene diphenyl diisocyanate; C57Bl/6 mice; Cross-reactivity; Occupational asthma