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• W1968888942 abstract "BackgroundYears after removal from exposure, workers with occupational asthma still show respiratory symptoms and airway hyperresponsiveness on re-exposure to the offending agent.ObjectiveWe investigated the persistence of the respiratory responsiveness to toluene diisocyanate (TDI) in a mouse model.MethodsBALB/C mice received dermal applications of TDI on days 1 and 8, and a single intranasal instillation of TDI on day 10, 15, 20, 25, 30, 40, 50, 60, or 90. After instillation, early (1 hour) changes in ventilatory function and methacholine responsiveness (22 hours) were assessed. Cell counts and macrophage inflammatory protein 2 were measured in bronchoalveolar lavage. Total serum IgE, IgG1, and IgG2a were quantified. Lymphocyte subpopulations were assessed in auricular and cervical lymph nodes, and release of IL-4 and IFN-γ by these lymph node cells was measured.ResultsToluene diisocyanate–treated mice showed immediate ventilatory changes, increased methacholine reactivity, and an influx of neutrophils and macrophage inflammatory protein 2 in bronchoalveolar lavage as long as 50 days after initial treatment. These mice also showed a relative increase in CD19+ cells and a decrease in CD4+ and CD8+ cells in auricular lymph nodes. Increased release of IL-4 and IFN-γ in auricular lymph node cells was observed only until 20 days after sensitization. Total serum IgE, IgG1, and IgG2a remained significantly elevated in TDI-sensitized mice until 90 days after dermal sensitization.ConclusionVentilatory and lung inflammatory responses decrease with increasing delay between sensitization and challenge, despite persistent humoral signs of sensitization. Years after removal from exposure, workers with occupational asthma still show respiratory symptoms and airway hyperresponsiveness on re-exposure to the offending agent. We investigated the persistence of the respiratory responsiveness to toluene diisocyanate (TDI) in a mouse model. BALB/C mice received dermal applications of TDI on days 1 and 8, and a single intranasal instillation of TDI on day 10, 15, 20, 25, 30, 40, 50, 60, or 90. After instillation, early (1 hour) changes in ventilatory function and methacholine responsiveness (22 hours) were assessed. Cell counts and macrophage inflammatory protein 2 were measured in bronchoalveolar lavage. Total serum IgE, IgG1, and IgG2a were quantified. Lymphocyte subpopulations were assessed in auricular and cervical lymph nodes, and release of IL-4 and IFN-γ by these lymph node cells was measured. Toluene diisocyanate–treated mice showed immediate ventilatory changes, increased methacholine reactivity, and an influx of neutrophils and macrophage inflammatory protein 2 in bronchoalveolar lavage as long as 50 days after initial treatment. These mice also showed a relative increase in CD19+ cells and a decrease in CD4+ and CD8+ cells in auricular lymph nodes. Increased release of IL-4 and IFN-γ in auricular lymph node cells was observed only until 20 days after sensitization. Total serum IgE, IgG1, and IgG2a remained significantly elevated in TDI-sensitized mice until 90 days after dermal sensitization. Ventilatory and lung inflammatory responses decrease with increasing delay between sensitization and challenge, despite persistent humoral signs of sensitization." @default.
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• W1968888942 date "2008-02-01" @default.
• W1968888942 modified "2023-10-17" @default.
• W1968888942 title "How long do the systemic and ventilatory responses to toluene diisocyanate persist in dermally sensitized mice?" @default.
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• W1968888942 doi "https://doi.org/10.1016/j.jaci.2007.09.006" @default.
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