Importance of Inflammatory and Immune Components in a Mouse Model of Airway Reactivity to Toluene Diisocyanate (TDI)

Details

• Personal Author:
  Karol MH ; Lange RW ; Lemus R ; Luster MI ; Matheson JM
• Description:
  BACKGROUND: Nearly 9 million individuals are exposed to agents in the workplace associated with asthma, and isocyanates represent the most common cause of occupationally induced asthma. OBJECTIVES: Nonetheless, the immunological mechanisms responsible for isocyanate-induced asthma are not clear. A murine model for toluene diisocyanate (TDI) asthma is described and employed to examine inflammatory and immune components that may be involved in the disease. METHODS: Groups (n = 6) of C57BL/6J and athymic mice were sensitized by subcutaneous injection (20 microl on day 1, 5 microl on days 4 and 11), and 7 days later challenged by inhalation (100 p.p.b., days 20, 22 and 24) with TDI. Twenty-four hours following the last challenge the tracheae and lungs were examined for histological changes as well as for the expression of Th1, Th2 and pro-inflammatory cytokines. Mice were also examined for airway reactivity to methacholine challenge and for specific and total IgE and IgG antibodies. RESULTS: TDI sensitization resulted in increased reactivity to methacholine challenge as well as a significant inflammatory response in the trachea and nares of wild-type mice, but not in the athymic mice nor in the lungs of the C57BL/6J mice. Airway inflammation was characterized by inflammatory cell influx, goblet cell metaplasia and epithelial damage. Histological changes in the trachea were accompanied by increased mRNA expression of interleukin (IL)-4, tumour necrosis factor alpha, lymphotoxin beta, lymphotactin and Rantes, as well as TDI-specific IgG antibodies and elevated levels of total IgE. IgE-specific antibodies were not detected with this exposure regimen but were produced when the TDI concentrations were increased. CONCLUSIONS: These studies provide a unique murine model for occupational asthma that generates both inflammatory and immune mediators similar to those occurring in TDI-induced asthma in humans. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Hypersensitivity Immune System Isocyanates Laboratories Lung Occupational Diseases Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Animal-studies Author Keywords: Airway Hypersensitivity Bronchial-asthma Immune-system Immunology Laboratory-animals Occupational-diseases Occupational-exposure Occupational Asthma Pulmonary-system-disorders Respiratory-system-disorders Toluene Diisocyanate

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• ISSN:
  0954-7894
• Publisher:
  Blackwell Science Ltd.
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Minnesota ; OSHA Region 3 ; OSHA Region 5 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  31
• Issue:
  7
• NIOSHTIC Number:
  nn:20021808
• Citation:
  Clin Exp Allergy 2001 Jul; 31(7):1067-1076
• Contact Point Address:
  Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Clinical and Experimental Allergy
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0e403a3b909e7b3d2aa5810cd4c6d9e7120c179086b5c4bf6924ba94b0cd23b43722a869c83320444299e0ea8b22e7baf618e4105b48dae9fee811d5af22538a
• Download URL:
  https://stacks.cdc.gov/view/cdc/198912/cdc_198912_DS1.pdf
• File Type:
  [PDF - 362.87 KB ]