A Novel Murine Model of Occupational Rhinitis Following Inhalation of Toluene Diisocyanate

Details

• Personal Author:
  Johnson VJ ; Luster MI ; Yucesoy, Berran
• Description:
  Diisocyanates are low molecular weight chemicals that have been identified as the leading cause of occupational asthma. Epidemiological evidence suggests that diisocyanate- induced rhinitis is a comorbid and often preceding condition in patients with occupational asthma. Understanding the pathogenesis of occupational rhinitis and its biological and chronological relationship with asthma will be critical for disease prevention. In this regard, we have developed a murine model of toluene diisocyanate (TDI)-induced rhinitis. Female C57BL/6 mice were exposed to TDI vapor via inhalation for 4 hours/day for 12 days with or without a 2 week rest period and TDI challenge. The nasal mucosa was examined after each experimental stage for alterations in cytokine expression and pathology. Mice exposed to TDI vapor for 2 weeks showed elevated expression of IL-4, IL-5, IL-13, IL-10 and IFNgamma suggesting a mixed Th1/Th2 immune response. Expression of proinflammatory cytokines (TNFalpha and IL-1beta) and adhesion molecules (VCAM-1 and ICAM-1) was also upregulated. These cytokine changes corresponded to a marked influx of inflammatory cells into the nasal mucosa, eosinophils being the predominant cell type. Removal from exposure for 2 weeks resulted in a reduction in cytokine expression and pathology to control levels. Subsequent challenge with TDI vapor resulted in robust upregulation of the same cytokine genes as well as eosinophilic inflammation. The present model shows that TDI inhalation induces allergic rhinitis displaying many of the cardinal features of human disease. Future work will use this model to define the immune mechanisms and also examine the temporal/dose relationship between TDI-induced rhinitis and asthma. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Chemistry Epidemiology Hypersensitivity Occupational Health Respiratory System Risk Assessment Risk Factors Safety

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• Keywords:
  Allergens Allergic-disorders Allergic-reactions Allergies Animal-studies Bronchial-asthma Chemical-analysis Chemical-composition Chemical-hypersensitivity Chemical-reactions Dose-response Drug-interaction Drug-receptor Inhalation-studies Mathematical-models Physical-reactions Risk-analysis Risk-factors Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; 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:
  96
• Issue:
  1
• NIOSHTIC Number:
  nn:20031926
• Citation:
  Toxicologist 2007 Mar; 96(1):281
• CAS Registry Number:
  Toluene (CAS RN 108-88-3)
• Federal Fiscal Year:
  2007
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:12bdcaae4450667c6733509f8fec56d10e882ebbb1062f99022e1d7a50419b331317cfd3ee302efec3803a00dd4741eaa238e7ca0c30e584057be790802bba01
• Download URL:
  https://stacks.cdc.gov/view/cdc/186036/cdc_186036_DS1.pdf
• File Type:
  [PDF - 168.62 KB ]