Interleukin-1 plays a critical role in airway inflammation and hyperresponsiveness in a murine model of toluene diisocyanate asthma.
Johnson-VJ; Yucesoy-B; Wang-W; Fluharty-K; Luster-MI
Proc Am Thorac Soc 2005 May; 2(Abstracts):A440
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.
Models; Bronchial-asthma; Laboratory-animals; Animals; Animal-studies; Airway-obstruction; Airway-resistance; Inhalation-studies; Lung-disorders; Pulmonary-system-disorders; Respiratory-system-disorders
Abstract; Conference/Symposia Proceedings
Issue of Publication
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Proceedings of the American Thoracic Society. 2005 ATS International Conference, May 20-25, 2005, San Diego, California