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舌下免疫疗法治疗屋尘螨变应原诱导的实验性变应性结膜炎的研究

Sublingual immunotherapy for experimental allergic conjunctivitis in a murine model induced by Dermatophagoides farinae allergen.

机构信息

Division of Research and Development, Wolwo Bio-Pharmaceutical Inc., Shanghai, PR China.

出版信息

Int Arch Allergy Immunol. 2013;161(3):205-12. doi: 10.1159/000346335. Epub 2013 Mar 15.

Abstract

BACKGROUND

Sublingual immunotherapy (SLIT) is a clinically effective treatment in allergic conjunctivitis (AC); however, the mechanism of the underlying pharmacodynamics remains unclear. Here, we investigate the efficacy and the mechanism of a sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine AC model.

METHODS

A murine model of AC caused by Der f extract was developed in BALB/c mice by repeated application of allergen. Sensitized mice were SLIT treated by Der f drops and subsequently analyzed for AC symptoms, histopathological and immunological parameters.

RESULTS

In this study, Der f extract successfully induced the symptoms of AC in BALB/c mice. In these sensitized mice, clinical symptoms (scratching behavior, lacrimation, conjunctival hyperemia and edema), immunological and histopathological findings (inflammatory cell infiltration) were very similar to those in human AC. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased the expression levels of total immunoglobulin E (IgE), Der f-specific IgE and T helper cell 2 (Th2) cytokine interleukin-4, with a significant increase in Der f-specific IgG4 and Th1 cytokine interferon-γ.

CONCLUSIONS

SLIT with Der f drops is a potentially effective means of immunotherapy for Der f-induced AC by modulating the Th2-biased allergic immune response.

摘要

背景

舌下免疫疗法(SLIT)是治疗过敏性结膜炎(AC)的一种临床有效方法;然而,其潜在的药效学机制尚不清楚。在这里,我们研究了一种经舌下给予粉尘螨(Der f)疫苗在小鼠 AC 模型中的疗效和机制。

方法

通过重复应用过敏原,在 BALB/c 小鼠中建立了由 Der f 提取物引起的 AC 小鼠模型。用 Der f 滴剂对致敏小鼠进行 SLIT 治疗,然后分析 AC 症状、组织病理学和免疫学参数。

结果

在这项研究中,Der f 提取物成功地诱导了 BALB/c 小鼠的 AC 症状。在这些致敏小鼠中,临床症状(搔抓行为、流泪、结膜充血和水肿)、免疫学和组织病理学发现(炎症细胞浸润)与人类 AC 非常相似。SLIT 治疗致敏小鼠可显著减轻临床和组织病理学症状,并降低总免疫球蛋白 E(IgE)、Der f 特异性 IgE 和辅助性 T 细胞 2(Th2)细胞因子白细胞介素-4 的表达水平,同时 Der f 特异性 IgG4 和 Th1 细胞因子干扰素-γ的表达水平显著增加。

结论

用 Der f 滴剂进行 SLIT 是通过调节 Th2 偏向性过敏免疫反应治疗 Der f 诱导的 AC 的一种潜在有效方法。

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