Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia.
J Leukoc Biol. 2012 Apr;91(4):557-69. doi: 10.1189/jlb.0711357. Epub 2012 Jan 31.
Asthma is recognized as a heterogeneous disorder, although in most patients, the clinical manifestations are effectively managed with established combination therapies. However, 5-10% of asthmatics have severe asthma, which does not respond to treatment, and these patients account for >50% of asthma-related healthcare costs. New investigations into the pathogenesis of glucocorticoid resistance in severe asthma indicate that pulmonary macrophages may play central roles in promoting airway inflammation, particularly in asthma that is resistant to steroid therapy. Importantly, factors that are linked to the activation of pulmonary macrophages may contribute to glucocorticoid resistance and severe asthma. Here, we review recent advances in understanding the roles of pulmonary macrophages in the mechanisms of glucocorticoid resistance and the pathogenesis of severe asthma. We discuss the role of macrophage phenotype, infection, IFN-γ, LPS, associated signaling pathways, TNF-α, MIF, and other macrophage-associated factors. Understanding the pathogenesis of steroid-resistant severe asthma will contribute to the identification of optimal therapeutic strategies for the effective management of the disease.
哮喘被认为是一种异质性疾病，尽管在大多数患者中，临床症状可以通过既定的联合疗法有效控制。然而，5-10%的哮喘患者患有严重哮喘，对治疗没有反应，而这些患者占哮喘相关医疗费用的>50%。对糖皮质激素抵抗严重哮喘发病机制的新研究表明，肺巨噬细胞可能在促进气道炎症中发挥核心作用，特别是在对类固醇治疗耐药的哮喘中。重要的是，与肺巨噬细胞激活相关的因素可能导致糖皮质激素抵抗和严重哮喘。在这里，我们综述了近年来对肺巨噬细胞在糖皮质激素抵抗机制和严重哮喘发病机制中的作用的理解进展。我们讨论了巨噬细胞表型、感染、IFN-γ、LPS、相关信号通路、TNF-α、MIF 和其他与巨噬细胞相关的因素的作用。了解类固醇抵抗性严重哮喘的发病机制将有助于确定最佳治疗策略，以有效管理该疾病。
