The Role of Tumor Necrosis Factor Alpha (TNF) in Toluene Diisocyanate (TDI) Asthma

Details

• Personal Author:
  Karol MH ; Lange JW ; Lemus R ; Luster MI ; Matheson JM
• Description:
  Nearly 9 million workers are exposed to chemical agents associated with occupational asthma with isocyanates representing the chemical class most responsible. Isocyanate-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. Isocyanate-induced asthma is characterized by airway inflammation and we hypothesized that inflammation is a prerequisite of isocyanate-induced asthma with tumor necrosis factor (TNF) a being critical to this process. To explore this hypothesis, TNFa receptor knockout (TNFR) and anti- TNFa antibody treated C57BU6J mice were sensitized by subcutaneous injection (20 microliters on day 1; 5 microliters, days 4 and 11), and challenged 7 days later by inhalation (100ppb; days 20, 22 and 24) with toluene diisocyanate (TDI). Airway inflammation, goblet cell metaplasia, epithelial cell damage and non-specific airway reactivity to methacholine challenge, measured 24 hrs following the last challenge were reduced to baseline levels in TNFa null mice. TNFa deficiency also markedly abrogated TDI-induced Th2 cytokines in airway tissues indicating a role in the development of Th2 responses. Intratracheal instillation studies (50 microliters, single dose, 0-58 mg/kg) with fluorescein-conjugated isothiocyanate (FITC) and intranasal studies (20 microliters, single dose, 0-10%) with TDI suggested that TNFa deficiency also resulted in a significant reduction in the migration of airway dendritic cells to the draining lymph nodes. Taken together, these results suggest that TNFa plays has multiple and central roles in TDI-induced asthma influencing both non-specific inflammatory processes as well as specific immune events. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Biological Factors Isocyanates Laboratories Occupational Exposure Occupational Health Respiratory Tract Diseases Safety Toluene Workplace

  More +
• Keywords:
  Airway-obstruction Animal-studies Biological-factors Bronchial-asthma Cell-damage Chemical-agent-detectors Diseases Laboratory-animals Occupational-exposure Pulmonary-system-disorders Respiratory-system-disorders Toluenes Work-environment Workers

  More +
• ISSN:
  0892-6638
• Publisher:
  Federation of American Societies for Experimental Biology
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• 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:
  15
• Issue:
  4
• NIOSHTIC Number:
  nn:20032185
• Citation:
  FASEB J 2001 Mar; 15(4):A664
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Editor(s):
  Whelan WJ
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Source Full Name:
  The FASEB Journal. Experimental Biology 2001, Orlando, Florida, March 13 - April 4, 2001
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6ed8489889bb805dc457bed801938e8a26eff8b47a45db5b353a2cd7d6222e01f2a1ef129a868327ad76d7efbd9db55077743e67f10bebeaa45ec89245d5a7b6
• Download URL:
  https://stacks.cdc.gov/view/cdc/186227/cdc_186227_DS1.pdf
• File Type:
  [PDF - 230.27 KB ]