Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model
Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model
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DOI：
10.4049/jimmunol.170.6.3289
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发表时间：
2003-03-15
影响因子：
4.4
通讯作者：
Sampson, HA
中科院分区：
文献类型：
--
作者：
Li, XM;Srivastava, K;Sampson, HA
花生过敏（PNA）是导致致命和近乎致命的食物过敏反应的主要原因。由于不良反应发生率高，使用花生 (PN) 蛋白的传统免疫疗法不适合 PNA 疗法。我们研究了 s.c. 的影响。注射工程化（修饰）的重组 PN 蛋白和热灭活的单核细胞增生李斯特菌 (HKLM) 作为 PN 过敏小鼠模型中过敏反应的佐剂。对 PN 过敏的 C3H/HeJ 小鼠进行皮下治疗。三种主要 PN 过敏原和 HKLM（改良的 (m)Ara h 1-3 加 HKLM）的混合物。确定了 PN 激发后对过敏反应的影响以及与 Ab 水平和细胞因子谱的关联。虽然都是。假治疗组的小鼠表现出过敏症状，中位症状评分为 3，仅 31%；而 mAra h 1-3 加 HKLM 组的小鼠出现轻度过敏反应，中位症状评分较低，为 0.5。核心体温、支气管收缩、血浆组胺和 PN 特异性 IgE 水平的变化均显着降低。这种保护作用明显比单独使用 mAra h 1-3 蛋白的治疗组更有效。单独使用 HKLM 并没有任何保护作用。仅在 mAra h 1-3 加 HKLM 处理的小鼠的脾细胞培养物中观察到 IL-5 和 IL-13 降低以及 IFN-γ 水平升高。这些结果表明，修饰 PN 蛋白和 HKLM 的免疫疗法可有效治疗该模型中的 PN 过敏，并且可能是治疗 PNA 的潜在方法。
Peanut allergy (PNA) is the major cause of fatal and near-fatal anaphylactic reactions to foods. Traditional immunotherapy using peanut (PN) protein is not an option for PNA therapy because of the high incidence of adverse reactions. We investigated the effects of s.c. injections of engineered (modified) recombinant PN proteins and heat-killed Listeria monocytogenes (HKLM) as an adjuvant on anaphylactic reactions in a mouse model of PN allergy. PN-allergic C3H/HeJ mice were treated s.c. with a mixture of the three major PN allergens and HKLM (modified (m)Ara h 1-3 plus HKLM). The effects on anaphylactic reactions following PN challenge and the association with Ab levels and cytokine profiles were determined. Although all. mice in the sham-treated groups exhibited anaphylactic symptoms with a median symptom score of 3, only 31%, of mice in the mAra h 1-3 plus HKLM group developed mild anaphylaxis, with a low median symptom score of 0.5. Alterations in core body temperature, bronchial constriction, plasma histamine, and PN-specific IgE levels were all significantly reduced. This protective effect was markedly more potent than in the mAra h 1-3 protein alone-treated group. HKLM alone did not have any protective effect. Reduced IL-5 and IL-13, and increased IFN-gamma levels were observed only in splenocytes cultures from mAra h 1-3 plus HKLM-treated mice. These results show that immunotherapy with modified PN proteins and HKLM is effective for treating PN allergy in this model, and may be a potential approach for treating PNA.