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Role of interleukin-1 in toluene diisocyanate asthma.
Johnson VJ; Yucesoy B; Luster MI
FASEB J 2004 Mar; 18(5)(II):A1130
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-1ß in the airways of mice with TDI asthma. We hypothesized that IL-1ß 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-1ß 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-1ß 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-1ß neutralization effectively prevented inflammation but only partially reduced AHR suggesting a possible role for IL-1a in this disease.
Respiratory-irritants; Respiratory-infections; Respiratory-system-disorders; Pulmonary-system-disorders; Pulmonary-disorders; Pulmonary-congestion; Occupational-exposure; Occupational-health; Animal-studies; Animals; Immune-system; Immune-system-disorders; Immune-reaction
Abstract; Conference/Symposia Proceedings
Issue of Publication
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The FASEB Journal, Experimental Biology 2004, Washington, DC, April 17-21, 2004
Page last reviewed: May 5, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division