Rhee Chae-Seo, Libet Lev, Chisholm Dugald, Takabayashi Kenji, Baird Stephen, Bigby Timothy D, Lee Chul Hee, Horner Anthony A, Raz Eyal
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Korea.
Immunology. 2004 Sep;113(1):106-13. doi: 10.1111/j.1365-2567.2004.01930.x.
While effective for the prevention and treatment of allergic rhinitis (AR) symptoms, currently available medications do not reverse allergen specific hypersensitivities. Therefore, pharmacotherapeutics are not curative and their daily use is often required for years. These investigations were conducted to determine whether immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) delivery protects previously sensitized mice from AR hypersensitivity responses and modulates their allergen specific immune profiles. Mice were first sensitized with ovalbumin (OVA) and alum, twenty-four hr before beginning a series of seven daily intranasal (i.n.) allergen challenges, subsets of mice received a single i.n. or intradermal (i.d.) dose of ISS-ODN or control oligodeoxynucleotide (C-ODN), a single intraperitoneal (i.p.) injection of dexamethasone (DXM), or no intervention. Mice receiving i.d. or i.n. ISS-ODN were found to have attenuated immediate and late phase effector cell responses to i.n. OVA challenge. Specifically, ISS-ODN treated mice had less histamine and cysteinyl leukotriene release and eosinophilic inflammation in their nasal passages than mice treated with C-ODN. In addition, splenocytes from ISS-ODN but not C-ODN treated mice displayed attenuated OVA-specific interleukin (IL)-4, IL-5, and IL-13 but increased interferon-gamma responses. Finally, ISS-ODN was generally a more effective treatment than DXM, both in blunting AR hypersensitivity responses and in shifting T helper 2 Th2-biased immune parameters towards Th1 dominance. As ISS-ODN delivery rapidly attenuated effector cell responses in this AR model in an allergen independent manner, the present results suggest that therapy with ISS-ODN alone may be an effective alternative to corticosteroid medications for the clinical management of AR.
虽然目前可用的药物对预防和治疗过敏性鼻炎（AR）症状有效，但并不能逆转过敏原特异性超敏反应。因此，药物治疗并非治愈性的，通常需要数年的每日用药。进行这些研究是为了确定免疫刺激序列寡脱氧核苷酸（ISS-ODN）给药是否能保护先前致敏的小鼠免受AR超敏反应，并调节其过敏原特异性免疫谱。首先用卵清蛋白（OVA）和明矾使小鼠致敏，在开始一系列为期七天的每日鼻内（i.n.）过敏原激发前24小时，将小鼠亚组接受单次鼻内或皮内（i.d.）剂量的ISS-ODN或对照寡脱氧核苷酸（C-ODN）、单次腹腔内（i.p.）注射地塞米松（DXM），或不进行干预。发现接受皮内或鼻内ISS-ODN的小鼠对鼻内OVA激发的即刻和迟发效应细胞反应减弱。具体而言，与用C-ODN处理的小鼠相比，用ISS-ODN处理的小鼠鼻腔中组胺和半胱氨酰白三烯释放减少，嗜酸性粒细胞炎症减轻。此外，来自用ISS-ODN而非C-ODN处理的小鼠的脾细胞显示OVA特异性白细胞介素（IL）-4、IL-5和IL-13反应减弱，但干扰素-γ反应增加。最后，在减弱AR超敏反应以及将T辅助细胞2（Th2）偏向的免疫参数转向Th1主导方面，ISS-ODN通常比DXM是更有效的治疗方法。由于在该AR模型中，ISS-ODN给药以过敏原独立的方式迅速减弱效应细胞反应，目前的结果表明，单独用ISS-ODN治疗可能是AR临床管理中皮质类固醇药物的有效替代方法。
