Epicutaneous Immunotherapy Using a New Epicutaneous Delivery System in Mice Sensitized to Peanuts
Epicutaneous Immunotherapy Using a New Epicutaneous Delivery System in Mice Sensitized to Peanuts
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DOI：
10.1159/000321822
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发表时间：
2011-01-01
影响因子：
2.8
通讯作者：
Benhamou, Pierre-Henri
中科院分区：
文献类型：
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作者：
Mondoulet, Lucie;Dioszeghy, Vincent;Benhamou, Pierre-Henri
背景：花生过敏是一种危及生命的疾病，人们期待新的有效且安全的治疗方法。我们评估了表皮免疫疗法（EPIT）作为过敏小鼠花生过敏的新替代疗法。方法：用花生蛋白提取物（PPE）与霍乱毒素混合灌胃致敏 60 只 BALB/c 小鼠。将涂有 100 μg PPE（Viaskin (R)，DBV Technologies，巴黎，法国）的表皮递送系统在 48 小时内每周应用于完整皮肤（EPIT；n = 20）。该组与经皮下免疫疗法治疗的致敏小鼠 (SCIT; n = 20)、未治疗的致敏小鼠 (sham, n = 20) 和幼稚小鼠 (naive; n = 20) 进行比较。 8周治疗后，进行组胺释放测试、通过体积描记法测量气道高反应性以及挑战后的阻力顺应性测量。对血液和支气管肺泡灌洗液进行取样以进行血清学、细胞因子和细胞学检查。结果：EPIT（0.26μg/ml）和SCIT（0.21μg/ml）组的特异性IgE（sIgE）在致敏后增加，而在治疗后下降（分别为0.09μg/ml，p <0.001和0.06μg/ml，p<0.001）。与假手术组相比，EPIT 组和 SCIT 组的 IgG1/IgG2a 比率降低（分别为 3.7；p < 0.001 和 2.7；p < 0.01 和 15.1）。在较高乙酰甲胆碱浓度下，EPIT 和 SCIT 组的增强暂停值低于假手术组（分别为 7.29、6.74 和 10.99，p < 0.01），并且与初始组（5.06）没有差异。与假手术组相比，治疗组的耐药顺从性发生了逆转（p
Background: Peanut allergy is a life-threatening condition for which new efficient and safe treatment is expected. We evaluated epicutaneous immunotherapy (EPIT) as a new alternative treatment for peanut allergy in sensitized mice. Methods: Sixty BALB/c mice were sensitized by gavages with peanut protein extract (PPE) mixed with cholera toxin. An epicutaneous delivery system, coated with 100 mu g PPE (Viaskin (R), DBV Technologies, Paris, France), was applied to intact skin every week during 48 h (EPIT; n = 20). This group was compared with sensitized mice treated with subcutaneous immunotherapy (SCIT; n = 20), untreated sensitized mice (sham, n = 20), and naive mice (naive; n = 20). After the 8-week treatment, a histamine release test, airway hyperreactivity measurement by plethysmography, and a resistance-compliance measurement after the challenge were performed. Blood and bronchoalveolar lavage were sampled for serology, cytokines, and cytology. Results: Specific IgE (sIgE) increased after sensitization in the EPIT (0.26 mu g/ml) and SCIT (0.21 mu g/ml) groups and decreased after treatment (0.09 mu g/ml, p < 0.001 and 0.06 mu g/ml, p < 0.001, respectively). The IgG1/IgG2a ratio decreased in the EPIT and SCIT groups versus the sham group (3.7; p < 0.001 and 2.7; p < 0.01 and 15.1, respectively). At the higher metacholine concentration, enhanced pause values were lower in the EPIT and SCIT groups than in the sham group (7.29, 6.74, and 10.99, p < 0.01, respectively), and did not differ from that of the naive group (5.06). Resistance-compliance was reversed in the treated groups versus the sham group (p