Type 1/type 2 cytokine paradigm and the progression of pulmonary fibrosis
Type 1/type 2 cytokine paradigm and the progression of pulmonary fibrosis
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DOI：
10.1378/chest.120.1_suppl.s5
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发表时间：
2001-07-01
期刊：
影响因子：
9.6
通讯作者：
Kunkel, SL
中科院分区：
文献类型：
--
作者：
Lukacs, NW;Hogaboam, C;Kunkel, SL
终末期慢性肺病的发病机制被认为是以最初的炎症反应为特征，随后是纤维增生和细胞外基质沉积。这些慢性肺部疾病中的许多具有多种共同特性，包括未知的病因学、不确定的起始和维持机制以及进行性纤维化。不幸的是，有效的治疗选择不容易用于治疗许多慢性肺部疾病，这可能反映了对这些疾病的科学和机制理解有限。然而，最近的研究表明，细胞因子网络可能在决定这些疾病的进展中起作用，因为这些介质可以在慢性纤维化肺病的维持期间影响成纤维细胞活化、增殖和胶原沉积。积累的数据支持这样的概念，即特定的细胞因子表型可能提供了一个基本的机制，调节或持续的纤维化过程。例如，干扰素-γ似乎抑制成纤维细胞活性，如增殖和胶原蛋白产生，而白细胞介素（IL）-4和IL-13可以增加成纤维细胞生长和胶原蛋白产生。有趣的是，这些介质是原型细胞因子，其在功能上定义1型或2型免疫应答。因此，以1型或2型反应为特征的细胞介导的肺部炎症的实验模型将有助于描述维持或解决慢性肺部炎症和伴随的纤维化的机制。
The pathogenesis of end-stage, chronic lung disease is thought to be characterized by an initial inflammatory response followed by fibroproliferation and deposition of extracellular matrix. Many of these chronic lung disorders share a variety of common properties, including an unknown etiology, undefined mechanisms of initiation and maintenance, and progressive fibrosis, Unfortunately, efficacious therapeutic options are not readily available for the treatment of many chronic lung diseases, which may reflect the limited scientific and mechanistic understanding of these disorders. However, recent studies have shown that cytokine networks are likely operative in dictating the progression of these diseases, as these mediators can influence fibroblast activation, proliferation, and collagen deposition during the maintenance of chronic fibrotic lung disease. Accumulating data support the concept that the specific cytokine phenotype may provide a fundamental mechanism for the regulation or continuation of the fibrotic process. For example, interferon-gamma appears to suppresses fibroblast activities, such as proliferation and collagen production, while interleukin (IL)-4 and IL-13 can augment fibroblast growth and collagen production. Interestingly, these mediators are prototypic cytokines that functionally define either a type-1 or a type-2 immune response. Thus, experimental models of cell-mediated lung inflammation, which are characterized by either a type-1 or a type-2 response, will be useful in delineating the mechanisms that either maintain or resolve chronic lung inflammation and accompanying fibrosis.