Interleukin-1 Plays a Critical Role in Airway Inflammation and Hyperresponsiveness in a Murine Model of Toluene Diisocyanate Asthma

Details

• Personal Author:
  Fluharty K ; Johnson VJ ; Luster MI ; Wang W ; Yucesoy, Berran
• Description:
  Interleukin-1 (IL-1) is a pleotropic cytokine that has been shown to play a prominent role in large molecular weight protein asthma in mice. IL-1 is also an important mediatory of eosinophil infiltration into the lung. Human studies have demonstrated increased IL-1 immunostaining in the submucosa of patients with toluene diisocyanate (TDI)-induced asthma and increased production of IL-1 evident in the airways of mice with TDI asthma. We hypothesized that IL-1 signaling plays a critical role in the pathogenesis of TDI asthma through regulation of airway inflammation. C57BL/6 mice were sensitized to TDI by vapor inhalation (20 ppb; 4hrs/day, 5 days/week, 6 weeks) and then challenged 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, consisting of lymphocytes and eosinophils as well as increased lung IL-4 expression. Mice deficient in IL-1 receptor type-1 (IL-1RI) did not show any increase in AHR nor airway inflammation. Airway inflammation was prevented in mice treated with neutralizing antibodies to IL-1B and IL-1. In contrast, antibodies to IL-1B and IL1a alone, only partially redcued AHR, whereas treatment of mice with IL-1B/IL-1a completely abolished AHR. TDI asthmatic mice showed increase lung expression of VCAM and ICAM, adhesion molecules important for the recruitment of eosinophils and lymphocytes and disruption of IL-1 signaling prevented this effect. These results suggest that IL-1 signaling is critical for the recruitment of inflammatory cells to the lung and AHR in TDI asthma. Increased expression of adhesion molecules represents a plausible mechanism. [Description provided by NIOSH]
• Subjects:
  Mining Occupational Health Safety
• Keywords:
  Airway-obstruction Airway-resistance Animal-studies Animals Bronchial-asthma Inhalation-studies Laboratory-animals Lung-disorders Models Pulmonary-system-disorders Respiratory-system-disorders

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• ISSN:
  1546-3222
• Publisher:
  American Thoracic Society
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• 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:
  2
• NIOSHTIC Number:
  nn:20029624
• Citation:
  Proc Am Thorac Soc 2005 May; 2(Abstracts):A440
• Federal Fiscal Year:
  2005
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the American Thoracic Society. 2005 ATS International Conference, May 20-25, 2005, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d47410795389a8b8bc93b542f58af4f960c56e8bdb24e784cc43dd2dcc3492d2b8421aed92cc0240a7924e95b8413f6b4e0fe288a2d4726d4265494eededca9a
• Download URL:
  https://stacks.cdc.gov/view/cdc/190564/cdc_190564_DS1.pdf
• File Type:
  [PDF - 585.47 KB ]