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Cellular and humoral factors in a subchronic model of toluene diisocyanate-induced (TDI) asthma.
Matheson-JM; Lemus-R; Karol-MH; Luster-MI
Am J Respir Crit Care Med 2003 Apr; 167(7):A716
Occupational asthma (OA) is responsible for 10 percent of all cases of asthma, and, diisocyanates, a chemical class with wide application in industry, are the most common low molecular weight chemicals responsible for OA. TDI-induced asthma has been difficult to diagnose and control, in part, because the biological mechanisms responsible for the disease and the determinants of exposure have not been well defined. We hypothesize that TDI-induced asthma can occur through immunological and non-immunological mechanisms; the mechanisms responsible being dependent upon the exposure paradigm. We have developed a low level, subchronic inhalation model to reflect the most common exposure paradigm in the workplace. C57BL/6 mice were sensitized to TDI by inhalation (20ppb, 4hrs/day, 5 days/week) for 6 weeks, and challenged by inhalation 14 days later (20ppb, 1hr). Sensitized/challenged mice displayed significant inflammation in the upper and lower airways, characterized by lymphocytes, neutrophils and eosinophils accompanied by goblet cell metaplasia, epithelial damage, serum specific IgG antibodies and non-specific airway hyperresponsiveness (AHR) to methacholine challenge. Significant increases in IL-4, IL-5 and IFN-y mRNA were measured in the airways. Adoptive transfer experiments demonstrated that both T and B lymphocytes as well as IgG antibodies are important in the TDI-induced airway hyperreactivity. Taken together, these results suggest that in a subchronic model, with a dose reflective of the current permissible workplace exposure level, that sensitization to TDI can occur under these conditions and demonstrates the importance of both a cellular and humoral response in the manifestation of TDI-induced asthma.
Models; Toluenes; Occupational-exposure; Pulmonary-system-disorders; Immunology; Airway-obstruction; Airway-resistance; Laboratory-animals; Animal-studies; Animals; Lymphocytes; Sensitization; Bronchial-asthma; Respiratory-system-disorders
Abstract; Conference/Symposia Proceedings
Issue of Publication
American Journal of Respiratory and Critical Care Medicine, 2003 International Conference, The American Thoracic Society, Seattle, WA, May 16-21, 2003
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division