Pratama Yusuf Alif, Dinina Fakhriyah, Nurhan Ahmad Dzulfikri, Sari Winda Fatma, Ardianto Chrismawan, Khotib Junaidi
Master Program of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia.
Bachelor Program of Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia.
Vet World. 2022 Sep;15(9):2333-2341. doi: 10.14202/vetworld.2022.2333-2341. Epub 2022 Sep 29.
Perennial allergic rhinitis (AR) is a chronic upper respiratory disease, with inflammation mediated by immunoglobulin E in the nasal mucosa caused by house dust mites. Recently, allergen immunotherapy showed promising allergic healing in patients with a definite history of sensitization. Based on this finding, a product was developed using Indonesian house dust mite (IHDM). This study aimed to optimize the allergenic rhinitis mouse model that was generated using IHDM to test the sensitivity and safety of this product.
Seven groups of mice were used for effectiveness testing - normal, negative control with IHDM challenge, positive control with 0.1% histamine challenge, and AR group by both IHDM-induced sensitization at 12.5, 50, 250, or 500 μg and IHDM challenge. Mice were sensitized by intraperitoneal administration of IHDM once a week for 3 consecutive weeks. Thereafter, the challenge was given intranasally 5 times on alternate days. The number of nose rubbing and sneezing was noted. Eosinophil infiltration was assessed histologically using hematoxylin and eosin staining. The expression of interleukin-5 (IL-5) mRNA in the nasal mucosa was determined using semi-quantitative reverse transcription-polymerase chain reaction.
The induction of AR with IHDM significantly increased the number of nose rubbing and sneezing in the mouse model. Eosinophil infiltration was observed in the nasal mucosa; however, no significant change occurred in the expression of IL-5 mRNA.
Overall, these data indicate that IHDM allergenic extract could be an effective sensitizing agent in a mouse model of AR. Although the use of IHDM is a limitation of this study because other sources of house dust mites might have different effects, this study provides a proper model for immunotherapy effectivity testing for pre-clinical studies.
常年性变应性鼻炎(AR)是一种慢性上呼吸道疾病,由屋尘螨引起鼻黏膜免疫球蛋白E介导的炎症。近来,变应原免疫疗法在有明确致敏史的患者中显示出有前景的变应性疾病治疗效果。基于这一发现,研发了一种使用印度尼西亚屋尘螨(IHDM)的产品。本研究旨在优化用IHDM建立的变应性鼻炎小鼠模型,以测试该产品的敏感性和安全性。
七组小鼠用于有效性测试——正常组、IHDM激发的阴性对照组、0.1%组胺激发的阳性对照组,以及分别用12.5、50、250或500μg IHDM诱导致敏并进行IHDM激发的AR组。小鼠每周腹腔注射IHDM一次,连续3周进行致敏。此后,隔天经鼻给予激发5次。记录蹭鼻和打喷嚏的次数。使用苏木精和伊红染色进行组织学评估嗜酸性粒细胞浸润情况。使用半定量逆转录聚合酶链反应测定鼻黏膜中白细胞介素-5(IL-5)mRNA的表达。
用IHDM诱导AR显著增加了小鼠模型中蹭鼻和打喷嚏的次数。在鼻黏膜中观察到嗜酸性粒细胞浸润;然而,IL-5 mRNA的表达未发生显著变化。
总体而言,这些数据表明IHDM变应原提取物可能是AR小鼠模型中的一种有效致敏剂。尽管使用IHDM是本研究的一个局限性,因为其他屋尘螨来源可能有不同影响,但本研究为临床前研究的免疫治疗有效性测试提供了一个合适的模型。