su-5614 and Inflammation

Isocyanate chemicals, including toluene diisocyanate (TDI), are currently the most common causes of occupational asthma. Although considerable controversy remains regarding its pathogenesis, TDI-induced asthma is characterized by hyperresponsiveness and inflammation of the airways. One of the histological hallmarks of inflammation is angiogenesis, but the possible role of vascular endothelial growth factor (VEGF), a potent angiogenic cytokine, in TDI-induced asthma is unknown. We developed a murine model to investigate TDI-induced asthma by performing two courses of sensitization with 3% TDI and one challenge with 1% TDI using ultrasonic nebulization to examine the potential involvement of VEGF in that disease. These mice develop the following typical pathophysiological features: airway hyperresponsiveness, airway inflammation, and increased VEGF levels in the airway. Administration of VEGFR inhibitors reduced all these pathophysiological symptoms. These results suggest that VEGF is one of the major determinants of TDI-induced asthma and that the inhibition of VEGF may be a good therapeutic strategy.

Topics: Administration, Inhalation; Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Migration Inhibition; Cell Movement; Disease Models, Animal; Endothelial Growth Factors; Extravasation of Diagnostic and Therapeutic Materials; Female; Indoles; Inflammation; Leukocyte Count; Lymphokines; Mice; Mice, Inbred BALB C; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Toluene 2,4-Diisocyanate; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors