Ke Xia, Huang Jiangju, Chen Quan, Hong Suling, Zhu Daoyin
Department of Otolaryngology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
Clin Invest Med. 2010 Jun 1;33(3):E196-202. doi: 10.25011/cim.v33i3.13726.
Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma.
BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma.
Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-gamma) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals.
Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.
过敏性哮喘的特征是由过敏原特异性辅助性T（Th）2细胞驱动的慢性气道炎症和气道高反应性。牛分枝杆菌卡介苗（BCG）接种已被证明在动物模型中可抑制Th2反应和过敏性气道炎症。由于白细胞介素（IL）-12能够抑制Th2反应，我们试图研究IL-12是否可作为佐剂来提高BCG接种预防过敏性哮喘的疗效。
将BALB/c新生小鼠（24只，48 - 72小时龄）随机分为3个亚组（每组n = 8），分别用PBS（对照）或含或不含表达IL-12的DNA质粒的BCG进行免疫。然后所有小鼠用卵清蛋白（OVA）致敏并激发，以建立过敏性哮喘模型。
与对照动物相比，单独接种BCG的小鼠气道炎症、支气管肺泡灌洗（BAL）液中嗜酸性粒细胞百分比和血清OVA特异性免疫球蛋白E（IgE）水平显著降低。BCG与IL-12联合使用时，其抑制作用显著增强。此外，相对于对照动物，单独接种BCG或IL-12的动物BAL液中IL-4产生减少，干扰素-γ（IFN-γ）产生增加。
我们的数据表明，BCG和IL-12联合接种在预防实验性过敏性气道炎症方面产生了良好效果，这可能是通过触发从Th2反应向Th1反应的转变来介导的。
