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经皮免疫治疗在过敏小鼠模型中使用新的传递系统进行完整皮肤。

Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy.

机构信息

DBV Technologies, Paris, France.

出版信息

Clin Exp Allergy. 2010 Apr;40(4):659-67. doi: 10.1111/j.1365-2222.2009.03430.x. Epub 2009 Dec 10.

Abstract

BACKGROUND

Allergen-specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods.

OBJECTIVE

Proof of concept of efficacy of EPIT on intact skin in mice sensitized to aeroallergens or food allergens.

METHODS

Mice were sensitized to pollen (n=18), house dust mite (HDM, n=24), ovalbumin (OVA, n=18) or peanut (n=18), and allocated to four groups: EPIT, SCIT, not treated (NT) and control. Specific Ig (sIg)E, sIgG1 and sIgG2a were monitored. After 8 weeks of treatment, plethysmography was performed after aerosol provocation with appropriate allergens.

RESULTS

At the highest doses of methacholine, pause enhancement (Penh) values were significantly decreased in the EPIT group vs. the sensitized NT groups (7.5 vs. 12.3 - pollen, 7.6 vs. 8.9 - HDM, 11.5 vs. 14.5 - OVA, 7.6 vs. 12.8 - peanut, respectively) (P<0.05). With all the allergens tested, Penh values were similar in SCIT, EPIT and control. IgG2a for pollen, HDM, OVA and peanuts were significantly increased in the EPIT group vs. NT: 0.97 vs. 0.42 microg/mL, 2.5 vs. 0.46 microg/mL, 0.39 vs. 0.05 microg/mL and 15.0 vs. 5.5 microg/mL, respectively (P<0.05). There were no significant differences between EPIT and SCIT groups. The IgE/IgG2a ratio decreased significantly in the EPIT group for the four allergens from 70 to 58 (pollen), 175 to 26 (HDM), 5433 to 120 (OVA) and 49 to 6 (peanut), respectively (P<0.05).

CONCLUSION

In mice sensitized to the four allergens tested, EPIT was as efficacious as SCIT, considered as the reference immunotherapy. These first results have to be confirmed by clinical studies.

摘要

背景

变应原特异性免疫疗法,皮下免疫疗法(SCIT)或口服免疫疗法,已经使用了近一个世纪,以重新引导过敏患者的不适当免疫反应。一种通过完整皮肤进行的新给药方式[表皮免疫疗法(EPIT)],使用原始的表皮传递系统,可能是这些经典方法的替代方法。

目的

证明在对气传过敏原或食物过敏原致敏的小鼠的完整皮肤上进行 EPIT 的疗效概念。

方法

将小鼠致敏于花粉(n=18)、屋尘螨(HDM,n=24)、卵清蛋白(OVA,n=18)或花生(n=18),并分为四组:EPIT、SCIT、未治疗(NT)和对照。监测特异性 Ig(sIg)E、sIgG1 和 sIgG2a。治疗 8 周后,用适当的过敏原进行气溶胶激发后进行体积描记术。

结果

在最高剂量的乙酰甲胆碱下,EPIT 组与致敏 NT 组相比,暂停增强(Penh)值显著降低(花粉为 7.5 对 12.3,HDM 为 7.6 对 8.9,OVA 为 11.5 对 14.5,花生为 7.6 对 12.8)(P<0.05)。用所有测试的过敏原,Penh 值在 SCIT、EPIT 和对照之间相似。花粉、HDM、OVA 和花生的 IgG2a 在 EPIT 组与 NT 组相比显著增加:0.97 对 0.42 μg/mL,2.5 对 0.46 μg/mL,0.39 对 0.05 μg/mL 和 15.0 对 5.5 μg/mL,分别(P<0.05)。EPIT 组与 SCIT 组之间无显著差异。对于四种过敏原,EPIT 组的 IgE/IgG2a 比值从 70 降至 58(花粉)、175 降至 26(HDM)、5433 降至 120(OVA)和 49 降至 6(花生),分别(P<0.05)。

结论

在对四种测试过敏原致敏的小鼠中,EPIT 与 SCIT 一样有效,被认为是参考免疫疗法。这些初步结果需要通过临床研究来证实。

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