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Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma.

Authors
Johnson-VJ; Yucesoy-B; Luster-MI
Source
J Allergy Clin Immunol 2005 Oct; 116(4):851-858
NIOSHTIC No.
20028553
Abstract
IL-1 is a pleotropic cytokine that has been shown to play a prominent role in asthma induced by large-molecular-weight proteins. Increased IL-1 immunostaining in the submucosa of patients with toluene diisocyanate (TDI)-induced asthma has also been observed, suggesting that this cytokine might also be important in asthma associated with low-molecular-weight chemicals. We sought to determine the role of IL-1 signaling in airway reactivity and inflammation by using a murine model of TDI-induced asthma. C57BL/6 mice were exposed to TDI by means of vapor inhalation (20 ppb; 4 hours per day, 5 days per week, for 6 weeks) and then challenged 2 weeks later by inhalation with 20 ppb TDI vapor for 1 hour. Sensitized-challenged mice showed increased airway hyperresponsiveness (AHR), increased levels of TDI-specific IgG1 antibodies, airway epithelial thickening, inflammation consisting of infiltrating lymphocytes and eosinophils, and increased mRNA expression of IL-4, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in the lung. Prevention of IL-1 signaling through deletion of the IL-1 receptor type I or administration of neutralizing antibodies to both IL-1beta and IL-1alpha abrogated the development of TDI-induced asthma. A partial reduction in AHR and TDI-specific IgG1 levels was observed in mice administered anti-IL-1beta, whereas anti-IL-1alpha had no effect on either parameter. Antibodies to IL-1beta or IL-1alpha alone blocked airway inflammation and the expression of IL-4 and adhesion molecules in the lung. These results suggest that IL-1 signaling is critical for AHR and airway inflammation, with IL-1beta and IL-1alpha having unique and overlapping roles in TDI-induced occupational asthma.
Keywords
Models; Bronchial-asthma; Toluenes; Airway-obstruction; Airway-resistance; Laboratory-animals; Animals; Animal-studies; Exposure-levels; Exposure-assessment
Contact
Victor J. Johnson, PhD, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd, Mail Stop 3014, Morgantown, WV 26505-2888
CODEN
JACIBY
Publication Date
20051001
Document Type
Journal Article
Email Address
vjohnson3@cdc.gov
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
0091-6749
NIOSH Division
HELD
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
Journal of Allergy and Clinical Immunology
State
WV
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