Kim Do Hyun, Kim Boo-Young, Shin Ji-Hyeon, Kim Sung Won, Kim Soo Whan
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Am J Otolaryngol. 2017 Mar-Apr;38(2):198-203. doi: 10.1016/j.amjoto.2017.01.008. Epub 2017 Jan 18.
The purpose of this study was to compare the anti-allergic effects of the combination of azelastine and mometasone with those of either agent alone in a Dermatophagoides farinae (Derf)-induced murine model of allergic rhinitis (AR).
Forty BALB/c mice were divided into five groups: azelastine (A), mometasone (M), a combination of azelastine and mometasone (MA), Derf, and control. Derf served as the allergen. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. The mucosal levels of mRNAs encoding interferon (IFN)-γ, T-bet, interleukin (IL)-4, GATA-3, Foxp3, IL-17, and ROR-γt were determined by real-time polymerase chain reaction. The T-bet, GATA-3, Foxp3, and ROR-γt results were confirmed by Western blotting.
Nose-rubbing motions; the levels of mRNAs encoding IL-4, GATA-3, and ROR-γt; and tissue eosinophil count were reduced in the MA compared with those in the Derf group (all P values <0.05). The levels of mRNAs encoding GATA3 and IL-4 mRNA [synthesized by T helper (Th)2 cells] were reduced and that of mRNA encoding Foxp3 was increased in the MA compared with those in the Derf and A groups. Western blotting confirmed these findings.
We found that the combination of intranasal azelastine and mometasone synergistically suppressed Th17 responses and (reciprocally) elevated Treg responses. Therefore, this combination not only ameliorated allergic inflammation by suppressing Th2 responses, but also usefully modified the Treg/Th17 balance.
本研究旨在比较氮卓斯汀和莫米松联合用药与单独使用任一药物在粉尘螨诱导的变应性鼻炎（AR）小鼠模型中的抗过敏作用。
将40只BALB/c小鼠分为五组：氮卓斯汀组（A）、莫米松组（M）、氮卓斯汀与莫米松联合用药组（MA）、粉尘螨组（Derf）和对照组。粉尘螨作为变应原。测量变应性症状评分、嗜酸性粒细胞计数和血清粉尘螨特异性IgE水平。通过实时聚合酶链反应测定编码干扰素（IFN）-γ、T-bet、白细胞介素（IL）-4、GATA-3、Foxp3、IL-17和ROR-γt的mRNA的黏膜水平。通过蛋白质印迹法确认T-bet、GATA-3、Foxp3和ROR-γt的结果。
与粉尘螨组相比，联合用药组的揉鼻动作、编码IL-4、GATA-3和ROR-γt的mRNA水平以及组织嗜酸性粒细胞计数均降低（所有P值<0.05）。与粉尘螨组和氮卓斯汀组相比，联合用药组中由辅助性T（Th）2细胞合成的编码GATA3和IL-4 mRNA的水平降低，而编码Foxp3的mRNA水平升高。蛋白质印迹法证实了这些结果。
我们发现鼻内使用氮卓斯汀和莫米松联合用药可协同抑制Th17反应并（相应地）提高调节性T细胞反应。因此，这种联合用药不仅通过抑制Th2反应改善了变应性炎症，而且有效地调节了调节性T细胞/Th17平衡。
