Affiliated First Hospital of Medical College, Zhejiang University, Hangzhou 310009, China.
Vaccine. 2012 Feb 14;30(8):1437-44. doi: 10.1016/j.vaccine.2012.01.005. Epub 2012 Jan 10.
Clinically, sublingual immunotherapy (SLIT) using allergen extracts effectively alleviates the symptoms of allergic rhinitis and asthma. We hypothesized that oral administration of a high-dose of allergen extracts imitates SLIT, which may prevent IgE-related responses in allergic diseases. In the present study, we investigated the effects of oral administration of allergen extracts from mugwort pollen (MP) on allergen-induced inflammation and airway hyperresponsiveness (AHR) in an allergic mouse model. After administration of MPdrop containing Art v 1 and Art v 4 extracts derived from MP specifically in MP-sensitized mice, the effects of MPdrop on AHR, inflammatory cell accumulation, cytokine production in the bronchoalveolar lavage fluid and lung tissue, and serum IgE and IgG levels were investigated. The results indicated that MPdrop not only prevented the AHR in response to methacholine in a dose-dependent manner but also significantly reduced the total serum and allergen-specific IgE levels. All of the maximal effects were achieved at a dose of 100μg/(kgd) and were comparable to the effects of dexamethasone at a dose of 0.5mg/(kgd). Furthermore, oral administration of MPdrop dose-dependently elevated allergen-specific serum IgG2a levels, reduced total and allergen-specific IgE levels and normalized the imbalance between the Th1 cytokine IL-12 and Th2 cytokines IL-4 and IL-5. Finally, oral administration of MPdrop significantly reduced goblet cell hyperplasia and eosinophilia in the MP-sensitized allergic mouse model. These data suggest that MPdrop effectively improves specific allergen-induced inflammation and AHR in MP-sensitized and -challenged mice and provides the rationale for clinical use of MPdrop in the specific allergen-induced asthma.
临床上，舌下免疫疗法（SLIT）使用过敏原提取物有效地缓解了过敏性鼻炎和哮喘的症状。我们假设口服高剂量的过敏原提取物模仿 SLIT，这可能预防 IgE 相关反应在过敏性疾病。在本研究中，我们调查了口服从艾蒿花粉（MP）过敏原提取物对过敏原诱导的炎症和气道高反应性（AHR）在过敏性小鼠模型。在含有 Art v 1 和 Art v 4 提取物的 MPdrop 给药后，专门从 MP 致敏的小鼠，MPdrop 对 AHR 的影响，炎症细胞的积累，在支气管肺泡灌洗液和肺组织中的细胞因子产生，和血清 IgE 和 IgG 水平进行了研究。结果表明，MPdrop 不仅预防了 AHR 对乙酰甲胆碱呈剂量依赖性，而且还显著降低了总血清和过敏原特异性 IgE 水平。所有的最大效果是在 100μg/（kgd）的剂量实现的，并且与地塞米松在 0.5mg/（kgd）的剂量的效果相当。此外，口服 MPdrop 剂量依赖性地升高过敏原特异性血清 IgG2a 水平，降低总和过敏原特异性 IgE 水平，并使 Th1 细胞因子 IL-12 与 Th2 细胞因子 IL-4 和 IL-5 之间的平衡正常化。最后，口服 MPdrop 显著减少杯状细胞增生和嗜酸性粒细胞在 MP 致敏的过敏性小鼠模型。这些数据表明，MPdrop 有效地改善了特定过敏原诱导的炎症和 AHR 在 MP 致敏和攻毒的小鼠，并提供了临床使用 MPdrop 在特定过敏原诱导的哮喘的原理。
