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

Details

• Personal Author:
  Karol MH ; Lange RW ; 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 pre-requisite of isocyanate-induced asthma with tumor necrosis factor (TNF) being critical to this process. To explore this hypothesis, TNF receptor knockout (TNFR) and anti TNF antibody treated C57BL/6J mice were sensitized by subcutaneous injection (20 ul on day 1; 5 ul, 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 TNF null mice. TNF deficiency also markedly abrogated TDI-induced Th2 cytokines in airway tissues indicating a role in the development of Th2 responses. Intratracheal instillation studies (50 ul, single dose, 0-58 mg/kg) with fluorescein-conjugated isothiocyanate (FITC) and intranasal studies (20 ul, single dose, 0-10%) with TDI suggested that TNF 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 TNF 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 Isocyanates Laboratories Lung Diseases Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety Toluene Workplace

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• 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

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• ISSN:
  1096-6080
• Publisher:
  Oxford University Press
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  60
• Issue:
  1
• NIOSHTIC Number:
  nn:20021388
• Citation:
  Toxicologist 2001 Mar; 60(1):174
• CAS Registry Number:
  Toluene (CAS RN 108-88-3)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ef65854d4fcfd22ab1757c12eda60ab4dc53107a2fb29d11c1e395143b5d2aea99f1b43b7ac020ab48382d969274c0dbca5144f73f6cfc6e3fa459625f4d9079
• Download URL:
  https://stacks.cdc.gov/view/cdc/198727/cdc_198727_DS1.pdf
• File Type:
  [PDF - 125.88 KB ]