Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis

Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis
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DOI:
10.1111/j.1365-2222.2006.02624.x
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发表时间:
2007-04-01
影响因子:
6.1
通讯作者:
Lund, K.
Lund, K.
中科院分区:
医学2区
文献类型:
--
作者:
Brimnes, J.;Kildsgaard, J.;Lund, K.

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背景:舌下免疫疗法(SLIT)是一种临床有效的治疗花粉和屋尘螨诱导的鼻炎和哮喘的方法。然而,这是由实现的机制尚不清楚。目的:本研究的目的是建立一个小鼠模型的鼻炎,以研究SLIT的效果和机制。方法:小鼠腹腔注射明矾吸附的草苔提取物致敏。致敏小鼠SLIT治疗,随后挑战鼻内和临床症状,抗体水平,嗜酸性粒细胞和T细胞response.Results分析:鼻内的致敏小鼠的挑战导致鼻炎的发展,其特征在于显着增加打喷嚏和流入的嗜酸性粒细胞到鼻子。特异性IgE水平在鼻咽灌洗液(NAL)中增加了五倍,在血清中增加了一倍以上。此外,在局部引流淋巴结中观察到辅助性T细胞2型(Th2)样T细胞应答。SLIT治疗致敏小鼠的NAL中的喷嚏、嗜酸性粒细胞增多和IgE水平降低了50%以上。此外,血清IgE和IgG1水平以及引流淋巴结中的T细胞反应也显著降低。治疗时间较短或剂量较低,只导致轻微的临床和免疫学参数的减少,表明SLIT的效果是时间和剂量dependent.Conclusion:在本研究中,我们已经建立了一个小鼠模型,显示使用临床相关的过敏原过敏性鼻炎的标志。使用该模型,我们已经证明SLIT治疗能够以时间和剂量依赖性方式减轻过敏症状。
Background: Sublingual immunotherapy (SLIT) is a clinically effective treatment in both pollen and house dust mite-induced rhinitis and asthma. However, the mechanisms by which this is accomplished are not clear.Objective: The objective of the current study was to establish a mouse model of rhinitis in order to study the effect and mechanisms of SLIT.Methods: Mice were sensitized by intraperitoneal injections of alum-adsorbed Phleum pratense extract. Sensitized mice were SLIT-treated and subsequently challenged intranasally and analysed for clinical symptoms, antibody levels, eosinophilia and T cell response.Results: Intranasal challenge of sensitized mice led to the development of rhinitis characterized by significantly increased sneezing and influx of eosinophils into the nose. Levels of specific IgE were fivefold increased in nasopharyngeal lavage (NAL) fluid and more than doubled in serum. Furthermore, a T-helper type 2 (Th2) like T cell response was observed in local draining lymph nodes. SLIT treatment of sensitized mice reduced sneezing, eosinophilia and IgE levels in the NAL by more than 50%. Moreover, serum levels of IgE and IgG1 as well as T cell response in the draining lymph nodes were also significantly reduced. Treatment for a shorter time or with a lower dose only led to minor reductions of the clinical and immunological parameters, indicating that the effect of SLIT is time and dose dependent.Conclusion: In the present study, we have established a mouse model displaying the hallmarks of allergic rhinitis using a clinically relevant allergen. Using this model, we have demonstrated that SLIT treatment is able to reduce allergic symptoms in a time- and dose-dependent manner.