药物干预过敏原诱发的哮喘
2012/12/25
摘要
空气过敏原是导致哮喘进展的最常见触发因素。近期的出生队列研究显示，空气过敏原致敏的患者，病毒感染是导致哮喘发生的危险因素。病毒感染通过调节气道粘膜树突状细胞，增强吸入性过敏症的免疫致病潜能。通过采用过敏原吸入激发临床模型，研究显示迟发型哮喘反应（LAR）与更明显的过敏原诱发的气道炎症和气道高反应性相关。气道嗜酸性粒细胞增多程度受到骨髓祖细胞和白介素-5的调节，且与LAR的幅度和高反应性增加相关。髓系和类浆细胞性树突状细胞亚型参与了过敏原诱导的LAR致病。髓性树突状细胞与过敏原诱导的炎症相关，而类浆细胞性树突状细胞在过敏原诱导的炎症消失中起到一定作用。通过采用过敏原吸入激发，已经在轻度哮喘患者中对许多潜在新哮喘治疗进行了评价，如吸入性反义寡核苷酸（TPI ASM8），通过抑制靶基因趋化因子受体3、白介素-3和白介素-5常见β链及粒细胞-巨噬细胞集落刺激因子受体的mRNA表达，抑制早期和迟发性LAR。抗人白介素-13抗体（IM-638）也能显著抑制早期和迟发性过敏原诱导的哮喘反应。Pitrakinra针对白介素-4和白介素-13，能显著抑制过敏原诱导的气道反应。过敏原诱发气道反应是评价新治疗对哮喘气道影响的很有价值的方法。
（刘国梁 审校）
Inflammopharmacology. 2012 Oct 25. [Epub ahead of print]
The pharmacological modulation of allergen-induced asthma.
Ma LL, O’Byrne PM.
Source
Firestone Institute of Respiratory Health, St. Joseph’s Healthcare, Department of Medicine, McMaster University, Hamilton, ON, Canada.
Abstract
Aeroallergens are the most common triggers for the development of asthma. Recent birth cohort studies have identified viral infections occurring against a background of aeroallergen sensitization as a potent risk factor for initiation of asthma. Viral infection enhances immunopathogenic potential of pre-existing inhalant allergy via modulating airway mucosal dendritic cells. By using an allergen inhalation challenge clinical model, studies have shown that the late asthma response (LAR) is associated with more pronounced allergen-induced airway inflammation and airway hyperresponsiveness. The degree of airway eosinophilia, regulated by bone marrow progenitor cells and interleukin-5 level, correlates with the magnitude of the LAR and the increase in hyperresponsiveness. Both myeloid and plasmacytoid dendritic cell subsets have been involved in the pathogenesis of allergen-induced LAR. Myeloid dendritic cells are responsible for the allergen presentation and induction of inflammation and plasmacytoid dendritic cells play a role in the resolution of allergen-induced inflammation. A variety of potential new classes of asthma medication has also been evaluated with the allergen inhalation challenge in mild asthmatic subjects. Examples are TPI ASM8, an inhaled anti-sense oligonucleotide drug product, which attenuated both early and LARs via inhibition of the target gene mRNA of chemokine receptor 3, and the common β chain of interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor receptor. Anti-human antibody interleukin-13 (IM-638) significantly attenuated both early and late allergen-induced asthma response. Pitrakinra, which targets both interleukin-4 and interleukin-13, substantially diminishes allergen-induced airway responses. Allergen-induced airway responses are a valuable way to evaluate the activity of possible new therapies in asthmatic airways.
Inflammopharmacology. 2012 Oct 25. [Epub ahead of print]
