Tsai Jaw-Ji, Yen Chung-Yang, Hsu Chun-Hsien, Yu Sheng-Jie, Chen Chao-Hsien, Liao En-Chih
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan.
Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan.
Allergy Asthma Clin Immunol. 2023 Apr 26;19(1):35. doi: 10.1186/s13223-023-00792-5.
Allergic asthma occurs worldwide and is particularly prevalent in westernized countries characterized by chronic airway inflammation resulting in airway hyperresponsiveness. The house dust mites (HDM) including Dermatophagoides pteronyssinus are major sources of sensitization and triggering allergic symptoms in asthmatic patients. The Der p 2 is a major allergen and the predominant source of causative respiratory disorders which induce airway inflammation and bronchial constriction in mite-allergic patients. Few studies evaluate the ameliorating effects of modified Liu-Wei-Di-Huang-Wan (modified LWDHW) on allergic asthma.
This study aimed to investigate the immunological mechanisms of modified LWDHW on the reductions of airway inflammation, signal transduction, inflammatory cytokine production, Th2 cell proliferation, and bronchial obstruction in Der p 2-induced asthmatic mice.
At least ten active ingredients were contained in the formula of modified LWDHW- 1217A and 1217B. Results showed that the immunoglobulin generations (Der p 2 specific- IgE and IgG1), inflammatory cytokine productions (IL-5 and IL-13) in the Sera and BALF could be down-regulated, and the Th1-cytokine productions (IL-12 and IFN-γ) be increased after immunotherapy with modified LWDHW of 1217A or 1217B. The inflammatory cell infiltrations (macrophages, eosinophils, and neutrophils) in the airway and the expressions of T2-related genes (IL-4, IL-5, and IL-13), T2-related transcription factor (GATA-3), and neutrophil chemotactic chemokine (IL-8) in the lung tissue of asthmatic mice were significantly decreased after the immunotherapy. The Th1/Th2 polarization had been identified that the IL-4/CD4 T cells were downregulated and IFN-γ/CD4 T cells were increased. The airway hyperresponsiveness to methacholine inhalation of Penh values was significantly decreased in the treated groups. There were significant improvements in the bronchus histopathology after immunotherapy with 1217A or 1217B which were evaluated by tracheal thickness, inflammatory cell count, and tracheal rupture of mouse lung.
It revealed that 1217A or 1217B could regulate the immune responses and improve pulmonary function. Data suggests that modified LWDHW of 1217A or 1217B have the potential for use as a therapeutic intervention for the treatment of mite allergen Der p 2-induced allergic asthma.
过敏性哮喘在全球范围内均有发生,在以慢性气道炎症导致气道高反应性为特征的西方国家尤为普遍。包括屋尘螨在内的尘螨是哮喘患者致敏和引发过敏症状的主要来源。Der p 2是一种主要过敏原,是导致呼吸道疾病的主要原因,可在螨过敏患者中诱发气道炎症和支气管收缩。很少有研究评估加味六味地黄丸(加味LWDHW)对过敏性哮喘的改善作用。
本研究旨在探讨加味LWDHW对降低Der p 2诱导的哮喘小鼠气道炎症、信号转导、炎性细胞因子产生、Th2细胞增殖和支气管阻塞的免疫机制。
加味LWDHW-1217A和1217B配方中至少含有十种活性成分。结果显示,用1217A或1217B加味LWDHW进行免疫治疗后,血清和支气管肺泡灌洗液中的免疫球蛋白生成(Der p 2特异性IgE和IgG1)、炎性细胞因子产生(IL-5和IL-13)可被下调,Th1细胞因子产生(IL-12和IFN-γ)增加。哮喘小鼠气道中的炎性细胞浸润(巨噬细胞、嗜酸性粒细胞和中性粒细胞)以及肺组织中T2相关基因(IL-4、IL-5和IL-13)、T2相关转录因子(GATA-3)和中性粒细胞趋化因子(IL-8)的表达在免疫治疗后显著降低。已确定Th1/Th2极化,即IL-4/CD4 T细胞下调,IFN-γ/CD4 T细胞增加。治疗组对吸入乙酰甲胆碱的气道高反应性Penh值显著降低。用1217A或1217B进行免疫治疗后,通过小鼠肺的气管厚度、炎性细胞计数和气管破裂评估,支气管组织病理学有显著改善。
结果表明,1217A或1217B可调节免疫反应并改善肺功能。数据表明,1217A或1217B加味LWDHW有潜力作为治疗螨过敏原Der p 2诱导的过敏性哮喘的治疗干预措施。