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.

Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice

“…In our animal model, the Co/Co-group responded more strongly to a methacholine provocation, with a pronounced decrease in FEV 0.1 , than the other mice. This is in agreement with the obstructive pattern of asthmatic murine models (8,25,39). To our knowledge, FEV 0.1 changes in response to methacholine challenge have not been assessed in an occupational asthma model.…”

Circulating miRs-183-5p, -206-3p and -381-3p may serve as novel biomarkers for 4,4’-methylene diphenyl diisocyanate exposure

“…The expression of Th1 Il-2 mRNA (Figure 1F) and Th2 Il-4 mRNA (Figure 1H) were not detectable in either MDI or vehicle control exposed ears whereas the Th2 Il-5 mRNA was not changed (Figure 1I). Given that the expression level of the α subunit of the high-affinity IgE receptor (Fc epsilon RI; FcεRI) in human mast cells and basophil has been found to be directly correlated with serum IgE levels (Gomez et al, 2007), and the presence of MDI-specific IgE or increase of total IgE level indicates that there is systemic sensitization to MDI (Wisnewski et al, 2011, Pollaris et al, 2016, we used FcεR1 mRNA expression in the ear as a measure of possible sensitization. FcεR1 mRNA was significantly increased 13.56-fold four days following 3 consecutive days of 1% MDI exposure (Figure 1K).…”

IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model

“…A deeper understanding of the disease is urgently needed to find more therapeutic targets. TDI-induced asthma is often characterised by accumulation of a large number of neutrophils and a smaller number of eosinophils in the airways [3]. Multiple mechanisms are thought to be involved in the induction of TDI-induced asthma, including immunological, genetic, neurogenic, etc., leading to the definition of two subtypes of TDI-induced asthma: immunological and nonimmunological [4].…”