Wang Weiwei, Yu Hongwei, Pan Yongliang, Shao Shengwen
Department of Anatomy, School of Medicine, Huzhou University, Huzhou, China.
Department of Histology and Embryology, School of Medicine, Huzhou University, Huzhou, China.
Am J Rhinol Allergy. 2021 Nov;35(6):809-816. doi: 10.1177/19458924211002604. Epub 2021 Mar 16.
Histamine H1 receptor (H1R) antagonists are the first-line drugs for the treatment of allergic rhinitis (AR) at present. Emerging evidence supports an important role of histamine H4 receptor (H4R) in allergic diseases. However, information regarding the effects of combined treatment with H1 and H4 receptor antagonists in AR is limited.
We aimed to assess the effects of combined treatment with H1R and H4R antagonists on Th2 inflammatory responses in the nasal mucosa of AR rats.
Sprague Dawley rats were sensitized with ovalbumin and treated with H1R antagonist desloratadine or/and H4R antagonist JNJ7777120. Western blotting was used to assay the phenotypic markers of mature dendritic cells in the nasal mucosa, including major histocompatibility complex class II (MHC-II) and co-stimulatory molecules CD80, CD86 and OX40 ligand (OX40L). Th2 inflammatory cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were determined by using enzyme-linked immunoassay.
The treatment with desloratadine alone down-regulated the CD86 expression, and decreased the production of Th2 cytokines, but had no impact on the expression of MHC-II, CD80 and OX40L. The administration of NJ7777120 alone reduced the levels of CD86, OX40L and Th2 cytokines, whereas MHC-II and CD80 expression was unaffected. The combination of desloratadine and JNJ7777120 showed more significant synergistic therapeutic effects than monotherapy.
H4R antagonist acted synergistically with H1R antagonist to reduce Th2 inflammatory responses by down-regulating CD86 and OX40L expression in the nasal mucosa of AR rats. The combination with H1R and H4R antagonists might be a new strategy for AR treatment.
组胺H1受体（H1R）拮抗剂是目前治疗变应性鼻炎（AR）的一线药物。新出现的证据支持组胺H4受体（H4R）在变应性疾病中起重要作用。然而，关于H1和H4受体拮抗剂联合治疗AR的效果的信息有限。
我们旨在评估H1R和H4R拮抗剂联合治疗对AR大鼠鼻黏膜Th2炎症反应的影响。
用卵清蛋白致敏Sprague Dawley大鼠，并用H1R拮抗剂地氯雷他定或/和H4R拮抗剂JNJ7777120进行治疗。采用蛋白质免疫印迹法检测鼻黏膜中成熟树突状细胞的表型标志物，包括主要组织相容性复合体II类（MHC-II）和共刺激分子CD80、CD86和OX40配体（OX40L）。采用酶联免疫吸附测定法测定鼻灌洗液中Th2炎症细胞因子，包括白细胞介素-4、5和13。
单独用地氯雷他定治疗可下调CD86表达，并降低Th2细胞因子的产生，但对MHC-II、CD80和OX40L的表达无影响。单独给予JNJ7777120可降低CD86、OX40L和Th2细胞因子水平，而MHC-II和CD80表达未受影响。地氯雷他定和JNJ7777120联合使用显示出比单一疗法更显著的协同治疗效果。
H4R拮抗剂与H1R拮抗剂协同作用，通过下调AR大鼠鼻黏膜中CD86和OX40L的表达来减轻Th2炎症反应。H1R和H4R拮抗剂联合使用可能是AR治疗的一种新策略。
