How long do the systemic and ventilatory responses to toluene diisocyanate persist in dermally sensitized mice?

• Published in: Journal of allergy and clinical immunology Vol. 121; no. 2; pp. 456 - 463.e5
• Main Authors: Vanoirbeek, Jeroen A.J., PhD, De Vooght, Vanessa, MSc, Vanhooren, Hadewijch M., MSc, Nawrot, Tim S., PhD, Nemery, Benoit, MD, PhD, Hoet, Peter H.M., PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2008; Elsevier; Elsevier Limited
• Subjects: Administration, Intranasal; Allergy and Immunology; Animals; Biological and medical sciences; Body Weight; Bronchoalveolar Lavage Fluid - chemistry; Bronchoconstrictor Agents; Chemokine CXCL2 - metabolism; dermal sensitization; Ear, External; Experiments; Fundamental and applied biological sciences. Psychology; Fundamental immunology; IFN-γ; IL-4; Immunization; Immunoglobulin E - blood; Immunoglobulin G - blood; Interferon-gamma - metabolism; Interleukin-4 - metabolism; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphocyte Subsets - pathology; lymphocyte subtypes; Male; Medical sciences; Methacholine Chloride; Mice; Mice, Inbred BALB C; MIP-2; Molecular weight; murine model; Neutrophils - pathology; occupational asthma; Olive oil; Respiration; Respiratory Hypersensitivity - complications; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - pathology; Respiratory Hypersensitivity - physiopathology; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin - immunology; Studies; TDI; Time Factors; Toluene 2,4-Diisocyanate - administration & dosage; Toluene 2,4-Diisocyanate - immunology; occupational asthma; MIP-2; IL-4; Airway hyperreactivity; Enhanced pause; dermal sensitization; Penh; Toluene diisocyanate; murine model; AHR; Concanavalin A; BAL; Macrophage inflammatory protein 2; AUC; Resistance; IFN-γ; OA; R; lymphocyte subtypes; Bronchoalveolar lavage; Area under the curve; TDI; ConA; Animal model; Interleukin 4; Immunology; Bronchus disease; Sensitization; Obstructive pulmonary disease; Lung disease; Immunopathology; Respiratory disease; Cytokine; Rodentia; Asthma; Vertebrata; Mammalia; Mouse; Animal; Skin; Derm; Lymphocyte; Macrophage inflammatory protein; Subtype; Occupational medicine; Gamma interferon
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.09.006

Background Years after removal from exposure, workers with occupational asthma still show respiratory symptoms and airway hyperresponsiveness on re-exposure to the offending agent. Objective We investigated the persistence of the respiratory responsiveness to toluene diisocyanate (TDI) in a mouse model. Methods 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. Results 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. Conclusion Ventilatory and lung inflammatory responses decrease with increasing delay between sensitization and challenge, despite persistent humoral signs of sensitization.