Lee Ki-Il, Bae Jun-Sang, Kim Eun Hee, Kim Ji Hye, Lyu Lele, Chung Young-Jun, Mo Ji-Hun
Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Konyang University College of Medicine, Daejeon, Korea.
Clin Exp Otorhinolaryngol. 2020 Nov;13(4):396-406. doi: 10.21053/ceo.2019.01837. Epub 2020 May 15.
Limited information is available regarding strain-related differences in mouse models of allergic rhinitis induced by Dermatophagoides farinae (Der f1). In this study, we compared differences between two mouse strains and determined the optimal dose of Der f1 for allergic rhinitis mouse models.
Forty-eight mice were assigned to the following six groups (n=8 per group): group A (control, BALB/c), group B (Der f1-sensitized BALB/c, 25 µg), group C (Der f1-sensitized BALB/c, 100 µg), group D (control, C57BL/6), group E (Der f1-sensitized C57BL/6, 25 µg), and group F (Der f1-sensitized C57BL/6, 100 µg). Allergic inflammation was induced with Der f1 and alum sensitization, followed by an intranasal challenge with Der f1. Rubbing and sneezing scores, eosinophil and neutrophil infiltration, and immunoglobulin, cytokine, and chemokine levels in the nasal mucosa and from splenocyte cultures were assessed.
Rubbing and sneezing scores were higher in groups B, C, E, and F than in groups A and D, with a similar pattern in both strains (i.e., group B vs. E and group C vs. F). Serum immunoglobulin levels were significantly elevated compared to the control in groups B and C, but not in groups E and F. Eosinophil and neutrophil infiltration increased (all P<0.05) after the Der f1 challenge (groups B, C, E, and F) compared to the control (groups A and D) in both the BALB/c and C57BL/6 strains, without any significant difference between the two strains (group A vs. D, group B vs. E, and group C vs. F) (P>0.05). BALB/c mice (group B) showed a greater elevation of splenic interleukin (IL)-4 (P<0.01), IL-5 (P<0.01), and IL-6 levels (P<0.05) and nasal IL-4 mRNA levels (P<0.001) than the C57BL/6 mice (group E). Interestingly, mice treated with 100 µg Der f1 showed a weaker allergic response than those treated with 25 µg.
We found 25 µg to be a more appropriate dose for Der f1 sensitization. BALB/c mice are more biased toward a Th2 response and are a more suitable model for allergic rhinitis than C57BL/6 mice. This study provides information on the appropriate choice of a mouse model for allergic rhinitis.
关于由粉尘螨(Der f1)诱导的变应性鼻炎小鼠模型中菌株相关差异的信息有限。在本研究中,我们比较了两种小鼠品系之间的差异,并确定了变应性鼻炎小鼠模型中Der f1的最佳剂量。
将48只小鼠分为以下六组(每组n = 8):A组(对照组,BALB/c)、B组(25μg Der f1致敏的BALB/c)、C组(100μg Der f1致敏的BALB/c)、D组(对照组,C57BL/6)、E组(25μg Der f1致敏的C57BL/6)和F组(100μg Der f1致敏的C57BL/6)。用Der f1和明矾致敏诱导变应性炎症,随后用Der f1进行鼻内激发。评估抓挠和喷嚏评分、嗜酸性粒细胞和中性粒细胞浸润以及鼻黏膜和脾细胞培养物中的免疫球蛋白、细胞因子和趋化因子水平。
B、C、E和F组的抓挠和喷嚏评分高于A和D组,两种品系的模式相似(即B组与E组、C组与F组)。与对照组相比,B组和C组的血清免疫球蛋白水平显著升高,但E组和F组未升高。与对照组(A组和D组)相比,在BALB/c和C57BL/6品系中,Der f1激发后(B、C、E和F组)嗜酸性粒细胞和中性粒细胞浸润增加(所有P<0.05),两种品系之间无显著差异(A组与D组、B组与E组、C组与F组)(P>0.05)。BALB/c小鼠(B组)脾脏白细胞介素(IL)-4(P<0.01)、IL-5(P<0.01)和IL-6水平(P<0.05)以及鼻内IL-4 mRNA水平(P<0.001)的升高幅度大于C57BL/6小鼠(E组)。有趣的是,用100μg Der f1处理的小鼠比用25μg处理的小鼠表现出较弱的变应性反应。
我们发现25μg是Der f1致敏更合适的剂量。与C57BL/6小鼠相比,BALB/c小鼠更倾向于Th2反应,是变应性鼻炎更合适的模型。本研究为变应性鼻炎小鼠模型的合适选择提供了信息。