Fu Chi-Ling, Chuang Ya-Hui, Chau Lee-Young, Chiang Bor-Luen
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Gene Med. 2006 Dec;8(12):1393-9. doi: 10.1002/jgm.974.
Allergic asthma strongly correlates with airway inflammation caused by cytokines secreted by allergen-specific type-2 T helper (Th2) cells, but the immunologic regulation of cell function is yet to be acquired. Further, IL-10 has been found to exert both antiinflammatory and immunoregulatory activities. This study aimed to elucidate the therapeutic effects of IL-10 administration via adenovirus-mediated gene delivery on airway inflammation in the ovalbumin (OVA)-induced murine model of asthma.
BALB/c mice were sensitized by intraperitoneal injections with OVA and challenged by nebulized OVA. The sensitized mice were given an intratracheal delivery of adenoviral vector expressing the murine IL-10 gene (AdIL-10), or mock adenoviral vector 4 days before the inhalation challenge of the OVA. Inflammatory parameters, such as the development of airway hyper-responsiveness (AHR), bronchial lavage fluid eosinophils, and chemokines were assayed.
Intratracheal administration of AdIL-10 could efficiently inhibit antigen-induced AHR and significantly decrease the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid of OVA-sensitized and challenged mice during the effector phase.
Our data showed that the intratracheal transfer of the IL-10 gene could affect the recruitment of inflammatory cells during the challenge phase in a way that would result in the inhibition of airway inflammation. These findings suggest that the development of an immunoregulatory strategy based on IL-10 might shed light on more effective treatment.
过敏性哮喘与变应原特异性2型辅助性T（Th2）细胞分泌的细胞因子所引起的气道炎症密切相关，但细胞功能的免疫调节机制尚未完全明确。此外，白细胞介素10（IL-10）已被发现具有抗炎和免疫调节活性。本研究旨在阐明通过腺病毒介导的基因传递给予IL-10对卵清蛋白（OVA）诱导的小鼠哮喘模型气道炎症的治疗作用。
通过腹腔注射OVA使BALB/c小鼠致敏，并用雾化OVA进行激发。在OVA吸入激发前4天，给致敏小鼠气管内注射表达小鼠IL-10基因的腺病毒载体（AdIL-10）或空腺病毒载体。检测气道高反应性（AHR）、支气管肺泡灌洗液嗜酸性粒细胞和趋化因子等炎症参数。
气管内给予AdIL-10可有效抑制抗原诱导的AHR，并在效应期显著减少OVA致敏和激发小鼠支气管肺泡灌洗液中嗜酸性粒细胞和中性粒细胞的数量。
我们的数据表明，气管内转移IL-10基因可在激发期影响炎症细胞的募集，从而抑制气道炎症。这些发现提示，基于IL-10的免疫调节策略的开发可能为更有效的治疗提供思路。
