Lack of Association of Antibodies with Diisocyanate-Induced Airway Inflammation, Hyperreactivity and Asthma

Details

• Personal Author:
  Karol MH ; Lange RW ; Lemus R ; Luster MI ; Matheson JM
• Description:
  Diisocyanates are the most frequent cause of chemically-induced occupational asthma. Chemically-induced asthma differs from occupational asthma caused by high molecular weight allergens, in that specific antibodies are rarely found in the sera of patients with chemically-induced asthma. To investigate the role of anitbodies in the pathogenesis of the disease we used both animal and human data. Mice deficient in tumor necrosis factor (TNF) activity, i.e., TNF receptor knockout animals and animals pretreated with TNF neutralizing antisera were exposed to toluene diisocyanate (TDI). We have shown that these animals fail to develop sensitization to TDI as evidenced by the absense of both airway inflammation and hyperractivity following TDI exposure. C57BL/6J mice were sensitized by sc injection and challenged on 3 occasions by inhalation of the chemical. Blood was drawn and sera were evaluated for TDI-specific IgE and IgG as well as for IgG subclasses. Using ELISA, TDI-specific IgE was not detected. TDI-specific IgG antibodies, with titers ranging from 800 - 1200, were found in all TDI-exposed groups. Antibodies were present in animals pretreated with anti-TNF antiserum, and in TNFR knockout animals, although these animals had either greatly diminished or no evidence of TDI asthma. In human studies, sera from 200 automobile painters were evaluated for hexamethylene diisocyanate (HDI)-specific antibodies. Thirty % of the painters had specific IgG antibodies, 4% had specific IgE antibodies, and 4% had clinically diagnosed asthma but none of the latter asthmatics had specific IgE. These results indicate the lack of association of antibodies with symptoms of asthma in an animal model and in humans. The results imply that diisocyanate asthma occurs through an antibody-independent mechanism. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Hypersensitivity Laboratories Lung Diseases Occupational Health Paint Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Airway Obstruction Allergens Animal Studies Exposure Levels Laboratory Animals Painters Pathogenesis Pulmonary System Disorders Respiratory System Disorders
• ISSN:
  1096-6080
• Publisher:
  Oxford University Press
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Connecticut ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 9 ; 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
• Pages in Document:
  8
• Volume:
  60
• Issue:
  1
• NIOSHTIC Number:
  nn:20021348
• Citation:
  Toxicologist 2001 Mar; 60(1):8
• Federal Fiscal Year:
  2001
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  Yale University, New Haven, Connecticut
• Peer Reviewed:
  False
• Start Date:
  19970901
• Source Full Name:
  The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
• End Date:
  20020831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8ea0ae49537ce782308f4e22b622c80e53f8b2cf3ff9303b68e2cdf548ad2e665023a05b1702cd7a936aa893be6ff1ddb100a685a6a9be8a28b9a3340dbc3e5f
• Download URL:
  https://stacks.cdc.gov/view/cdc/198706/cdc_198706_DS1.pdf
• File Type:
  [PDF - 127.14 KB ]