Th1 and Th2 responses regulate experimental lung granuloma development.
Th1 and Th2 responses regulate experimental lung granuloma development.
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发表时间：
1996-09
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通讯作者：
S. L. Kunkel;N. Lukacs;Robert M. Strieter;S. Chensue
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作者：
S. L. Kunkel;N. Lukacs;Robert M. Strieter;S. Chensue
慢性间质性肺疾病的发病机制通常以强烈的炎症反应为特征，伴有纤维增生和细胞外基质沉积。某些肺部疾病具有共同特征，包括病因不明、发病和维持机制不明确以及终末期纤维化。进行性肺部炎症可发生在特发性肺纤维化和终末期结节病等疾病中，与大量发病率和死亡率相关。不幸的是，没有有效的治疗方法来治疗这些疾病，这反映出对这些疾病的科学认识有限。然而，细胞因子网络很可能在决定这些疾病的进展中起作用。最近的研究表明，在慢性纤维化肺病的发展过程中，多种细胞因子影响成纤维细胞的活化、增殖和胶原沉积。特别是，γ干扰素抑制成纤维细胞的增殖和胶原蛋白的产生，而白细胞介素-4增强成纤维细胞的生长和胶原蛋白的产生。有趣的是，这两种介质是典型的细胞因子，它们在功能上定义Th1或Th2反应。因此，以Th1或Th2反应为特征的肉芽肿性肺炎症的实验模型将有助于描述维持和解决慢性肉芽肿性肺炎症的机制。这些实验系统将被证明是特别重要的，因为慢性肺部炎症发病过程中的炎症程度和成纤维细胞活化/增殖可能取决于疾病演变过程中表达的Th1-和th2样细胞因子的平衡。
The pathogenesis of chronic interstitial lung disease is often characterized as an intense inflammatory response with accompanying fibroproliferation and deposition of extracellular matrix. Certain of these lung disorders share common characteristics, including an unknown etiology, ill defined mechanisms of initiation and maintenance, and end-stage fibrosis. Progressive pulmonary inflammation, as can occur in diseases such as idiopathic pulmonary fibrosis and end-stage sarcoidosis, is associated with substantial morbidity and mortality. Unfortunately, efficacious therapeutic options are not available for the treatment of these diseases, reflecting the limited scientific understanding of these disorders. However, it is likely that cytokine networks are operative in dictating the progression of these diseases. Recent studies show that various cytokines affect fibroblast activation, proliferation, and collagen deposition during the evolution of chronic fibrotic lung disease. In particular, gamma interferon suppresses such fibroblast activities as proliferation and collagen production, while interleukin-4 augments fibroblast growth and collagen production. Interestingly, these two mediators are the prototypic cytokines which functionally define either a Th1 or a Th2 response. Thus, experimental models of granulomatous lung inflammation, which are characterized by either a Th1 or a Th2 response, will be useful in delineating the mechanisms which maintain and resolve chronic granulomatous lung inflammation. These experimental systems will prove to be especially important as the degree of inflammation and fibroblast activation/proliferation during the pathogenesis of chronic pulmonary inflammation may be dependent upon a balance of Th1- and Th2-like cytokines which are expressed during the evolution of the disease.