A murine model of toluene diisocyanate–induced asthma can be treated with matrix metalloproteinase inhibitor

• Published in: Journal of allergy and clinical immunology 2001-12, Vol.108 (6), p.1021-1026
• Main Authors: Lee, Yong Chul, Song, Chang Ho, Lee, Heung Bum, Ohc, Jong-Lark, Rhee, Yang Keun, Park, Hae Sim, Koh, Gou Young
• Format: Article
• Language: English
• Subjects: airway hyperresponsiveness; Allergic diseases; Animals; asthma; Asthma - chemically induced; Asthma - drug therapy; Biological and medical sciences; Bronchoalveolar Lavage Fluid - cytology; Disease Models, Animal; Female; Immunopathology; matrix metalloproteinase; Matrix Metalloproteinase 9 - physiology; Matrix Metalloproteinase Inhibitors; Medical sciences; Mice; Mice, Inbred BALB C; Protease Inhibitors - therapeutic use; Respiratory and ent allergic diseases; Toluene 2,4-Diisocyanate - toxicity; Toluene diisocyanate
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2001.120132

Background: Toluene diisocyanate (TDI) is a leading cause of occupational asthma. TDI-induced asthma is an inflammatory disease of the airways that is associated with airway remodeling. However, there are little data available on the role of matrix metalloproteinases (MMPs) in TDI-induced asthma. Objective: We evaluated whether MMP-9 participates in the airway inflammation in TDI-induced asthma. An additional aim of the present study was to determine whether MMP inhibitors could be effective therapeutic agents for TDI-induced asthma. Methods: We developed a murine model of TDI-induced asthma to examine the involvement of MMPs by performing 2 sensitizations with 3% TDI and 1 challenge with 1% TDI using ultrasonic nebulization. Results: Murine TDI-induced asthma includes findings of (1) increased inflammatory cells, including neutrophils, lymphocytes, and eosinophils; (2) histologic changes, including infiltration of inflammatory cells around bronchioles, thickened airway epithelium, and accumulation of mucus and debris in the bronchioles; (3) increased MMP-9 activity in inflammatory cells in the airway lumen; and (4) airway hyperresponsiveness. Administration of an MMP inhibitor remarkably reduced all these pathophysiologic findings. Conclusion: We conclude that TDI-induced occupational asthma is associated with the induction of MMP-9 in inflammatory cells, and the inhibition of MMP-9 may be a good therapeutic strategy. (J Allergy Clin Immunol 2001;108:1021-6.)