Cohn Lauren, Elias Jack A, Chupp Geoffrey L
Yale University School of Medicine, Section of Pulmonary and Critical Care Medicine, New Haven, Connecticut, USA.
Annu Rev Immunol. 2004;22:789-815. doi: 10.1146/annurev.immunol.22.012703.104716.
When asthma is diagnosed, eosinophilic inflammation and airway remodeling are established in the bronchial airways and can no longer be separated as cause and effect because both processes contribute to persistence and progression of disease, despite anti-inflammatory therapy. Th2 cells are continually active in the airways, even when disease is quiescent. IL-13 is the key effector cytokine in asthma and stimulates airway fibrosis through the action of matrix metalloproteinases on TGF-beta and promotes epithelial damage, mucus production, and eosinophilia. The production of IL-13 and other Th2 cytokines by non-T cells augments the inflammatory response. Inflammation is amplified by local responses of the epithelium, smooth muscle, and fibroblasts through the production of chemokines, cytokines, and proteases. Injured cells produce adenosine that enhances IL-13 production. We review human and animal data detailing the cellular and molecular interactions in established allergic asthma that promote persistent disease, amplify inflammation, and, in turn, cause disease progression.
哮喘被诊断时，支气管气道中已存在嗜酸性粒细胞炎症和气道重塑，且二者不再能区分为因果关系，因为尽管进行了抗炎治疗，但这两个过程均会导致疾病的持续和进展。即使疾病处于静止期，Th2细胞在气道中仍持续活跃。IL-13是哮喘中的关键效应细胞因子，它通过基质金属蛋白酶对转化生长因子-β的作用刺激气道纤维化，并促进上皮损伤、黏液分泌和嗜酸性粒细胞增多。非T细胞产生IL-13和其他Th2细胞因子会增强炎症反应。上皮细胞、平滑肌细胞和成纤维细胞通过产生趋化因子、细胞因子和蛋白酶的局部反应放大炎症。受损细胞产生腺苷，增强IL-13的产生。我们综述了人类和动物数据，详细阐述了已确诊的过敏性哮喘中促进疾病持续、放大炎症进而导致疾病进展的细胞和分子相互作用。
