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

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BACKGROUND: 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. OBJECTIVES: Evaluating the effect of long-term respiratory isocyanate exposure - with or without prior dermal exposure- on sensitization, inflammatory responses and airway hyperreactivity (AHR). METHODS: 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. RESULTS: 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. CONCLUSION: Dermal exposure to TDI determines airway hyperreactivity after repeated airway exposure to TDI.
Tijdschrift: Toxicology
ISSN: 0300-483X
Volume: 421
Pagina's: 84 - 92
Jaar van publicatie:2019
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:1
CSS-citation score:1
Authors from:Higher Education
Toegankelijkheid:Closed