Dermal exposure determines the outcome of repeated airway exposure in a long-term chemical-induced asthma-like mouse model

• Published in: Toxicology (Amsterdam) Vol. 421; pp. 84 - 92
• Main Authors: Pollaris, Lore, Van Den Broucke, Sofie, Decaesteker, Tatjana, Cremer, Jonathan, Seys, Sven, Devos, Fien C., Provoost, Sharen, Maes, Tania, Verbeken, Erik, Vande Velde, Greetje, Nemery, Benoit, Hoet, Peter H.M., Vanoirbeek, Jeroen A.J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.06.2019
• Subjects: Administration, Cutaneous; Administration, Intranasal; Airway hyperreactivity; Animals; Asthma - chemically induced; Asthma - immunology; Asthma - pathology; Asthma - physiopathology; Balb/c mice; Bronchoalveolar Lavage Fluid - immunology; Cytokines - blood; Cytokines - immunology; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Disease Models, Animal; IgE; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunoglobulin G - blood; Immunoglobulin G - immunology; Leukocytes - drug effects; Leukocytes - immunology; Lung - drug effects; Lung - immunology; Lung - pathology; Lung - physiology; Lymph Nodes - drug effects; Lymph Nodes - immunology; Male; Mice; Mice, Inbred BALB C; Th2/Th1 response; Toluene 2,4-Diisocyanate - administration & dosage; Toluene diisocyanate; Airway hyperreactivity; Toluene diisocyanate; Balb/c mice; Th2/Th1 response; Dendritic cells; IgE
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2019.05.001

Exposure to diisocyanates is an important cause of occupational asthma (OA) in the industrialized world. Since OA occurs after long-term exposure to diisocyanates, we developed a chronic mouse model of chemical-induced asthma where toluene diisocyanate (TDI) was administered at two different exposure sites. Evaluating the effect of long-term respiratory isocyanate exposure - with or without prior dermal exposure- on sensitization, inflammatory responses and airway hyperreactivity (AHR). On days 1 and 8, BALB/c mice were dermally treated (20 μl/ear) with 0.5% 2,4-toluene diisocyanate TDI or the vehicle acetone olive oil (AOO) (3:2). Starting from day 15, mice received intranasal instillations with 0.1% TDI of vehicle five times in a week, for five successive weeks. One day after the last instillation airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and structural lung changes. Immune-related parameters were assessed in the lungs (BAL and tissue), blood, cervical- and auricular lymph nodes. Mice repeatedly intranasally exposed to TDI showed systemic sensitization and a mixed Th1/Th2 type immune response, without the presence of AHR. However, when mice are first dermally sensitized with TDI, followed by repeated intranasal TDI challenges, this results in a pronounced Th2 response and AHR. Dermal exposure to TDI determines airway hyperreactivity after repeated airway exposure to TDI.