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Toluene diisocyanate and methylene diphenyl diisocyanate: asthmatic response and cross-reactivity in a mouse model

  • Immunotoxicology
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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.

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Acknowledgments

This work was supported by a grant of the Interuniversity Attraction Poles Program-Belgian State-Belgian Science Policy [IUAP P7/30].

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    Authors and Affiliations

    1. Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Herestraat 49 mailbox 706, 3000, Leuven, Belgium

      Lore Pollaris, Fien Devos, Vanessa De Vooght, Benoit Nemery, Peter H. M. Hoet & Jeroen A. J. Vanoirbeek

    2. Laboratory of Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, 3000, Leuven, Belgium

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    1. Lore Pollaris
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    Correspondence to Jeroen A. J. Vanoirbeek.

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    Lore Pollaris and Fien Devos have contributed equally to this article.

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    Pollaris, L., Devos, F., De Vooght, V. et al. Toluene diisocyanate and methylene diphenyl diisocyanate: asthmatic response and cross-reactivity in a mouse model. Arch Toxicol 90, 1709–1717 (2016). https://doi.org/10.1007/s00204-015-1606-6

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