Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts
Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts
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DOI：
10.1016/j.alit.2016.05.012
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发表时间：
2017-01-01
影响因子：
6.8
通讯作者：
Kikuchi, Toshiaki
中科院分区：
文献类型：
--
作者：
Shima, Ienjiro;Koya, Toshiyuki;Kikuchi, Toshiaki
背景：舌下免疫治疗(SIT)作为一种过敏原免疫治疗方法已受到重视。然而，缝隙形成的机理还没有得到充分的研究。因此，我们评估了Sit在小鼠哮喘模型中的作用，该模型通过鼻内注射屋尘螨(HDM)提取物致敏。方法：雌性BALB/c小鼠鼻内暴露HDM 3或5周(每周连续5天)。小鼠被给予低剂量(0.5毫克/天)或高剂量(5毫克/天)的HDM舌下提取物2周，然后再鼻腔暴露一周。检测气道高反应性(AHR)、支气管肺泡灌洗液(BALF)细胞计数、BALF和淋巴结细胞培养上清液中细胞因子水平以及过敏原特异性抗体。结果：在致敏5周的小鼠中，大剂量Sit可改善AHR、气道嗜酸性粒细胞增多和杯状细胞化生。在致敏3周的小鼠中，即使是低剂量的Sit也能改善AHR和气道嗜酸性粒细胞增多。Sit高剂量组小鼠颌下淋巴结细胞培养上清液中Th2细胞因子水平降低，而IL-10水平升高。致敏3周或5周的小鼠BALF中总IgA升高，高剂量的Sit也使致敏5周的小鼠变应原特异性IgG2a升高。结论：HDM致敏小鼠早期诱导Sit可明显抑制AHR和杯状细胞化生。过敏原特异性IgG2a和局部IgA的调节可能在AHR和气道炎症的改善中起作用。版权所有(C)2016，日本过敏学会。爱思唯尔B.V.制作和主办。
Background: Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts.Methods: Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or high-dose (5 mg/day) sublingual HDM extracts for 2 weeks, followed by an additional week of intranasal exposure. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, cytokine levels in the BALF and lymph node cell culture supernatants, and allergen-specific antibodies were measured. Lung histology was also investigated.Results: In mice sensitized for 5 weeks, high-dose SLIT ameliorated AHR, airway eosinophilia and goblet cell metaplasia. In mice sensitized for 3 weeks, even low dose SLIT ameliorated AHR and airway eosinophilia. Th2 cytokine levels in culture supernatants of submandibular lymph node cells in high dose SLIT mice decreased, whereas IL-10 levels increased. Total IgA in BALF increased in mice sensitized for 3 or 5 weeks, and high-dose SLIT also increased allergen-specific IgG2a in mice sensitized for 5 weeks.Conclusions: These data suggest that earlier induction of SLIT in HDM-sensitized mice provides superior suppression of AHR and goblet cell metaplasia. The modulation of allergen specific IgG2a and local IgA might play a role in the amelioration of AHR and airway inflammation. Copyright (C) 2016, Japanese Society of Allergology. Production and hosting by Elsevier B.V.