Kim Jiyoun, Remick Daniel G
Department of Surgery, University of Michigan School of Medicine, 2120 Taubman Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0344, USA.
Curr Allergy Asthma Rep. 2007 May;7(2):151-6. doi: 10.1007/s11882-007-0013-3.
Asthma is a unique form of chronic airway inflammation characterized by reversible airway obstruction, airway hyperresponsiveness and the production of specific inflammatory mediators. Local activation of both immune and nonimmune cells in the lung triggers the release of these immunomodulator molecules. Among them, tumor necrosis factor (TNF)-alpha, a multipotent pro-inflammatory mediator, plays a critical role in immunoregulation of asthma by contributing to bronchopulmonary inflammation and airway hyperresponsiveness. Blocking TNF-alpha activity has already shown outstanding efficacy in other chronic inflammatory diseases including rheumatoid arthritis, Crohn's disease, and psoriasis. The successful treatment of these other chronic inflammatory diseases provides hope that TNF inhibitors may have application for the treatment of asthma. Recent developments in animal models and clinical trials in patients with severe asthma provide strong support for the concept that blocking TNF-alpha activity represents a new approach in asthma therapy. In this review, we address the multipotential role of TNF-alpha in asthma and the efficacy and safety of TNF-alpha blocking agents in asthma.
哮喘是一种独特的慢性气道炎症形式，其特征为可逆性气道阻塞、气道高反应性以及特定炎症介质的产生。肺内免疫细胞和非免疫细胞的局部激活触发了这些免疫调节分子的释放。其中，肿瘤坏死因子（TNF）-α作为一种多效性促炎介质，通过促进支气管肺部炎症和气道高反应性，在哮喘的免疫调节中发挥关键作用。在包括类风湿性关节炎、克罗恩病和牛皮癣在内的其他慢性炎症性疾病中，阻断TNF-α活性已显示出显著疗效。这些其他慢性炎症性疾病的成功治疗为TNF抑制剂可能应用于哮喘治疗带来了希望。在重度哮喘动物模型和患者临床试验中的最新进展，为阻断TNF-α活性代表哮喘治疗新方法这一概念提供了有力支持。在本综述中，我们阐述了TNF-α在哮喘中的多方面作用以及TNF-α阻断剂在哮喘治疗中的疗效和安全性。
