Xie Qiang-min, Wu Ximei, Wu Hui-min, Deng Yang-mei, Zhang Shui-juan, Zhu Jian-ping, Dong Xin-wei
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration, Medical Science College of Zhejiang University, 388 Yuhangtang Rd. Hangzhou City, Zhejiang Province 310058, PR China.
Int Immunopharmacol. 2008 Dec 10;8(12):1639-45. doi: 10.1016/j.intimp.2008.07.015. Epub 2008 Aug 20.
Clinically sublingual immunotherapy (SLIT) by using allergen extracts effectively alleviates the symptoms of allergic rhinitis and asthma. Supposed that oral administration of high-dose of allergen extracts imitates SLIT and may prevent IgE-related responses in allergic diseases, we investigated the effects of oral administration of allergen extracts from Dermatophagoides farinae (Derf) on allergen-induced inflammation and airway hyperresponsiveness (AHR) in a model of asthmatic rat. After administration to the specific Derf-sensitized rats with Derfdrop solution containing Derf1 and Derf2 extracts derived from Derf, the effects of Derfdrop on AHR, inflammatory cell accumulation, cytokine production in the bronchoalveolar lavage fluid and lung tissue, as well as serum IgE and IgG levels were investigated. Results indicated that Derfdrop not only dose-dependently prevented the AHR in response to methacholine, but also significantly reduced the serum total and allergen-specific IgE levels, all the maximal effects were achieved at dose of 5 mg/kg/d, and were as comparable as those of dexamethasone at dose of 1.0 mg/kg/d. Furthermore, oral administration of Derfdrop not only dose-dependently elevated allergen-specific serum IgG levels and reduced total and allergen-specific IgE levels, but also normalized the imbalance between the Th1 cytokine, IFN-gamma and Th2 cytokine, IL-4. Finally, oral administration of Derfdrop significantly reduced Goblet cell hyperplasia and eosinophilia in the Derf-sensitized allergic rat model. These data suggest that Derfdrop effectively improves specific allergen-induced inflammation and AHR in Derf-sensitized and -challenged rats and provide with the rationale for clinical SLIT by using Derfdrop in a specific allergen-induced asthma.
临床上,使用变应原提取物进行舌下免疫疗法(SLIT)可有效缓解过敏性鼻炎和哮喘的症状。假设口服高剂量变应原提取物可模拟SLIT并可能预防过敏性疾病中与IgE相关的反应,我们研究了口服粉尘螨变应原提取物对哮喘大鼠模型中变应原诱导的炎症和气道高反应性(AHR)的影响。在用含有源自粉尘螨的Derf1和Derf2提取物的Derfdrop溶液给予特定的粉尘螨致敏大鼠后,研究了Derfdrop对AHR、炎症细胞积聚、支气管肺泡灌洗液和肺组织中细胞因子产生以及血清IgE和IgG水平的影响。结果表明,Derfdrop不仅剂量依赖性地预防了对乙酰甲胆碱的AHR,还显著降低了血清总IgE和变应原特异性IgE水平,所有最大效应均在5mg/kg/d的剂量下实现,且与1.0mg/kg/d剂量的地塞米松相当。此外,口服Derfdrop不仅剂量依赖性地提高了变应原特异性血清IgG水平并降低了总IgE和变应原特异性IgE水平,还使Th1细胞因子IFN-γ和Th2细胞因子IL-4之间的失衡恢复正常。最后,口服Derfdrop显著减少了粉尘螨致敏的过敏性大鼠模型中的杯状细胞增生和嗜酸性粒细胞增多。这些数据表明,Derfdrop可有效改善粉尘螨致敏和激发的大鼠中特定变应原诱导的炎症和AHR,并为在特定变应原诱导的哮喘中使用Derfdrop进行临床SLIT提供了理论依据。