Role of Interleukin-1 in Toluene Diisocyanate Asthma

Details

• Personal Author:
  Johnson VJ ; Luster MI ; Yucesoy, Berran
• Description:
  Diisocyanates are the leading cause of occupational asthma. Numerous human studies have implicated the immune system in the pathogenesis of diisocyanate asthma and increased interleukin-1 (IL-1) immunostaining is evident in the submucosa. We and others have demonstrated increased production of IL-1β in the airways of mice with TDI asthma. We hypothesized that IL-1β plays a critical role in the pathogenesis of TDI asthma. C57BL/6 mice were sensitized to TDI by vapor inhalation (20 ppb; 4hrs/day, 5 days/week, 6 weeks) and then challenged 2 weeks later by inhalation of 20 ppb TDI vapor for 1 hr. Sensitized/challenged mice showed increased airway hyperresponsiveness (AHR) to methacholine challenge and a TDI-specific late asthmatic reaction 4-5 hours following challenge. Significant airway inflammation was also evident. Pulmonary expression of IL-1β and IL-4 mRNA was also increased following challenge. Mice deficient in IL-1 receptor type I did not show any increase in AHR, airway inflammation or cytokine expression. Systemic administration of neutralizing antibody to IL-1β 24 hours prior to challenge only partially reduced AHR but blocked leukocyte recruitment and cytokine gene expression in the airways. These results suggest that IL-1 signaling is an important mediator of TDI asthma. IL-1β neutralization effectively prevented inflammation but only partially reduced AHR suggesting a possible role for IL-1a in this disease. [Description provided by NIOSH]
• Subjects:
  Animals Immune System Irritants Lung Lung Diseases Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Animal-studies Immune-reaction Immune-system Immune-system-disorders Occupational-exposure Occupational-health Pulmonary-congestion Pulmonary-disorders Pulmonary-system-disorders Respiratory-infections Respiratory-irritants Respiratory-system-disorders

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• ISSN:
  0892-6638
• 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:
  18
• Issue:
  5
• NIOSHTIC Number:
  nn:20025079
• Citation:
  FASEB J 2004 Mar; 18(5)(II):A1130
• CAS Registry Number:
  Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Federal Fiscal Year:
  2004
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  False
• Part Number:
  II
• Source Full Name:
  The FASEB Journal, Experimental Biology 2004, Washington, DC, April 17-21, 2004
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ab25b2f0f8c1b750cbbb34856922d49bc0559cf7f59918e9a3c09c3a050bac6a2217a86deb71766b408e3bc0eb5e72ca8a8ba1581830058797ea34094054672c
• Download URL:
  https://stacks.cdc.gov/view/cdc/196581/cdc_196581_DS1.pdf
• File Type:
  [PDF - 318.09 KB ]