Oh Chad K, Raible Donald, Geba Gregory P, Molfino Nestor A
MedImmune, LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
Inflamm Allergy Drug Targets. 2011 Jun;10(3):180-6. doi: 10.2174/187152811795564073.
Asthma is a complex disease characterized by variable airflow limitation, hyperresponsiveness, and airways inflammation. Despite valuable therapeutic advances to control asthma symptoms in the last decade, a quantifiable proportion of patients with moderate to severe asthma continue to experience inadequate disease control, highlighting an important unmet need. In animal models of asthma, interleukin (IL)-9 regulates the development of airway inflammation, mucus production, airway hyperresponsiveness, and airway fibrosis largely by increasing mast cell numbers and activity in the airways. Mast cells are involved in the pathogenesis of eosinophilic and noneosinophilic asthma. Thus, targeting the IL-9 pathway may provide a new therapeutic modality for asthma. The purpose of this review is to summarize the IL-9-mast cell axis in the pathogenesis of asthma and discuss clinical studies with a humanized anti-IL-9 monoclonal antibody, MEDI-528, in subjects with asthma.
哮喘是一种复杂的疾病，其特征为气流受限、高反应性和气道炎症。尽管在过去十年中在控制哮喘症状方面取得了宝贵的治疗进展，但仍有相当比例的中重度哮喘患者疾病控制不佳，这凸显了一个重要的未满足需求。在哮喘动物模型中，白细胞介素（IL）-9主要通过增加气道中肥大细胞的数量和活性来调节气道炎症、黏液分泌、气道高反应性和气道纤维化的发展。肥大细胞参与嗜酸性粒细胞性和非嗜酸性粒细胞性哮喘的发病机制。因此，靶向IL-9通路可能为哮喘提供一种新的治疗方式。本综述的目的是总结IL-9-肥大细胞轴在哮喘发病机制中的作用，并讨论使用人源化抗IL-9单克隆抗体MEDI-528对哮喘患者进行的临床研究。
