Hayashi Toshiharu, Hasegawa Keiko, Sasaki Yuji
Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753-8515, Japan.
Inflammation. 2008 Feb;31(1):47-56. doi: 10.1007/s10753-007-9048-9. Epub 2007 Sep 12.
Oligodeoxynucleotides (ODN) with CpG motifs (CpG ODN) induce T helper (Th)1-type reaction. We aimed to evaluate the therapeutic effect of CpG ODN in the development of late allergic rhinitis induced by ovalbumin (OVA), which is one of Th2 diseaes, in BALB/c mice. Effects of a single dose of synthetic CpG-ODN (50 microg) intraperitoneally (i.p.) at the priming phase (on day 0) by OVA on the development of late eosinophilic rhinitis at respiratory areas were compared to the control mice treated with its vehicle (ODN without CpG motifs; 50 microg). Animals were again sensitized by OVA (on day 10) i.p., and 4 days after second sensitization animals were challenged by OVA intranasally (on day 14). Four days after challenge, eosinophilic reactions, nasal lesions and local cytokine values were examined. Compared to the control group, the CpG ODN-administration increased production of OVA-specific Th1 cytokine (interferon-gamma) and decreased productions of ovalubmin-specific Th2 cytokines [interleukin (IL)-5 and IL-13] in nasal cavity fluids, supernatants of splenocytes and/or sera. Also, eosinophilia and increased total IgE values were decreased in mice treated with the CpG ODN compared to the control group. Moreover, nasal lesions with infiltration of eosinophils were prominently reduced by the CpG ODN-treatment compared to the control mice. The present study suggests that the systemic administration of CpG ODN at the priming phase may reduce local OVA-specific Th2 responses, resulting in decreased nasal pathology in the late allergic eosinophilic rhinitis.
含CpG基序的寡脱氧核苷酸(ODN)(CpG ODN)可诱导辅助性T细胞(Th)1型反应。我们旨在评估CpG ODN对BALB/c小鼠中由卵清蛋白(OVA)诱导的迟发性变应性鼻炎(其为Th2疾病之一)发展的治疗效果。将在致敏阶段(第0天)腹腔内(i.p.)单次注射合成的CpG-ODN(50微克)对呼吸道区域迟发性嗜酸性粒细胞性鼻炎发展的影响,与用其赋形剂(不含CpG基序的ODN;50微克)处理的对照小鼠进行比较。动物在第10天再次通过腹腔注射OVA致敏,在第二次致敏后4天通过鼻内给予OVA对动物进行激发(第14天)。激发后4天,检查嗜酸性粒细胞反应、鼻病变和局部细胞因子值。与对照组相比,给予CpG ODN可增加鼻腔液体、脾细胞上清液和/或血清中OVA特异性Th1细胞因子(干扰素-γ)的产生,并减少卵清蛋白特异性Th2细胞因子[白细胞介素(IL)-5和IL-13]的产生。此外,与对照组相比,用CpG ODN处理的小鼠中嗜酸性粒细胞增多和总IgE值升高的情况有所减少。而且,与对照小鼠相比,CpG ODN处理显著减轻了伴有嗜酸性粒细胞浸润的鼻病变。本研究表明,在致敏阶段全身给予CpG ODN可能会降低局部OVA特异性Th2反应,从而减少迟发性变应性嗜酸性粒细胞性鼻炎的鼻病理学变化。