Lee Yong C, Kwak Yong-Geun, Song Chang H
Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Chonju, South Korea.
J Immunol. 2002 Apr 1;168(7):3595-600. doi: 10.4049/jimmunol.168.7.3595.
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.
异氰酸酯类化学物质，包括甲苯二异氰酸酯（TDI），是目前职业性哮喘最常见的病因。尽管关于其发病机制仍存在相当大的争议，但TDI诱发的哮喘的特征是气道高反应性和炎症。炎症的组织学特征之一是血管生成，但是血管内皮生长因子（VEGF），一种有效的血管生成细胞因子，在TDI诱发的哮喘中可能发挥的作用尚不清楚。我们建立了一个小鼠模型，通过使用超声雾化器用3%的TDI进行两个疗程的致敏和用1%的TDI进行一次激发来研究TDI诱发的哮喘，以检查VEGF在该疾病中的潜在作用。这些小鼠出现以下典型的病理生理特征：气道高反应性、气道炎症以及气道中VEGF水平升高。给予VEGFR抑制剂可减轻所有这些病理生理症状。这些结果表明，VEGF是TDI诱发哮喘的主要决定因素之一，抑制VEGF可能是一种良好的治疗策略。
