Anti-inflammatory activity of sublingual immunoglobulin (SLIG) in a murine model of allergen-driven airway inflammation
Anti-inflammatory activity of sublingual immunoglobulin (SLIG) in a murine model of allergen-driven airway inflammation
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DOI：
10.1016/j.vaccine.2012.06.049
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发表时间：
2012-08-17
期刊：
影响因子：
5.5
通讯作者：
Moingeon, P.
中科院分区：
文献类型：
--
作者：
Batard, T.;Zimmer, A.;Moingeon, P.
目的：静脉注射免疫球蛋白（IVIG）在多种疾病中具有抗炎作用。人类皮下注射抗ige对严重持续性过敏性哮喘有好处。鉴于舌下过敏原免疫治疗呼吸道I型过敏的疗效已得到证实，我们研究了舌下免疫球蛋白（SLIG），尤其是抗ige SLIG，在过敏原驱动的气道炎症小鼠模型中的治疗潜力。方法：用大鼠单克隆IgG1或IgG2a对BALB/c小鼠进行舌下处理，或直接针对小鼠IgE，或无特异性报道。气道高反应性（AHR）通过全身容积描记术评估，嗜酸性粒细胞浸润在支气管肺泡灌洗（BAL）中表现。分别通过ELISA或CBA检测细胞因子的产生，分析ova特异性抗体和T细胞在血清、唾液或肺和引流淋巴结中的反应。结果：无论AHR和BAL对小鼠IgE的特异性如何，舌下颗粒OVA（阳性对照）处理的小鼠以及接受各种大鼠IgG1的小鼠中，AHR和BAL嗜酸性粒细胞浸润量均显著降低。相比之下，用PBS（阴性对照）或各种大鼠IgG2a治疗的小鼠没有观察到改善。SLIG抗炎活性与Th2下调无关。Th17或诱导Foxp3(+) CD4（+）调节性T细胞反应。质谱分析表明，大鼠IgG1和IgG2a的不同功效与它们与口服免疫细胞携带的凝集素相互作用的能力无关。结论：在过敏原驱动的气道炎症小鼠模型中，在没有过敏原的情况下，与免疫球蛋白特异性无关，SLIG表现出抗炎活性。SLIG作为一种非侵入性的方法，值得进一步研究其作为治疗过敏性哮喘以外其他炎症性疾病的方法。(C) 2012 Elsevier Ltd.版权所有。
Aim: Intravenous immunoglobulin (IVIG) displays anti-inflammatory activities in many diseases. Subcutaneous administration of anti-IgE in humans provides benefit in severe persistent allergic asthma. Given the well established efficacy of sublingual allergen immunotherapy in respiratory type I allergies, we investigated the therapeutic potential of sublingual immunoglobulin (SLIG), most particularly anti-IgE SLIG, in a murine model of allergen-driven airway inflammation.Methods: BALB/c mice sensitized with ovalbumin (OVA) were treated sublingually with rat monoclonal IgG1 or IgG2a, either directed to mouse IgE or with no reported specificity. Airway hyperresponsiveness (AHR) was assessed by whole body plethysmography, and eosinophil infiltrates were characterized in bronchial alveolar lavages (BAL). OVA-specific antibody and T cell responses were analyzed in sera and saliva or lung and draining lymph nodes, by ELISA or CBA measurement of cytokine production, respectively.Results: AHR and BAL eosinophil infiltrates were substantially decreased in mice treated sublingually with particulate OVA (positive control), as well as in animals receiving various rat IgG1, irrespective of their specificity for murine IgE. In contrast, no improvement was observed in mice treated with PBS (negative control) or various rat IgG2a. SLIG anti-inflammatory activity is not related to a downregulation of Th2. Th17 or an induction of Foxp3(+) CD4(+) regulatory T cell responses. Mass spectrometry analysis of glycan moieties, such as sialic acid, suggests that the differential efficacy of rat IgG1 and IgG2a is not related to their capacity to interact with lectins borne by oral immune cells.Conclusions: In a murine model of allergen-driven airway inflammation, SLIG exhibits an anti-inflammatory activity irrespective of the immunoglobulin specificity, and in the absence of allergen. As a noninvasive approach, SLIG deserves to be further studied as a treatment for other inflammatory diseases beyond allergic asthma. (C) 2012 Elsevier Ltd. All rights reserved.