Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Pharmacol Rev. 2012 Apr;64(2):337-58. doi: 10.1124/pr.111.004622. Epub 2012 Mar 8.
During the last decade, significant research has been focused on Toll-like receptors (TLRs) in the pathogenesis of airway diseases. TLRs are pattern recognition receptors that play pivotal roles in the detection of and response to pathogens. Because of the involvement of TLRs in innate and adaptive immunity, these receptors are currently being exploited as possible targets for drug development. Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which innate and adaptive immunity play an important role. To date, asthma is the most common chronic disease in children aged 5 years and older. COPD is prevalent amongst the elderly and is currently the fifth-leading cause of death worldwide with still-growing prevalence. Both of these inflammatory diseases result in shortness of breath, which is treated, often ineffectively, with bronchodilators and glucocorticosteroids. Symptomatic treatment approaches are similar for both diseases; however, the underlying immunological mechanisms differ greatly. There is a clear need for improved treatment specific for asthma and for COPD. This review provides an update on the role of TLRs in asthma and in COPD and discusses the merits and difficulties of targeting these proteins as novel treatment strategies for airway diseases. TLR agonist, TLR adjuvant, and TLR antagonist therapies could all be argued to be effective in airway disease management. Because of a possible dual role of TLRs in airway diseases with shared symptoms and risk factors but different immunological mechanisms, caution should be taken while designing pulmonary TLR-based therapies.
在过去的十年中，大量的研究集中在 Toll 样受体 (TLRs) 在气道疾病发病机制中的作用。TLRs 是模式识别受体，在病原体的检测和反应中起着关键作用。由于 TLRs 参与固有和适应性免疫，这些受体目前正被开发为药物靶点。哮喘和慢性阻塞性肺疾病 (COPD) 是慢性炎症性气道疾病，固有和适应性免疫在其中起着重要作用。迄今为止，哮喘是 5 岁及以上儿童中最常见的慢性疾病。COPD 在老年人中较为常见，目前是全球第五大致死原因，其发病率仍在上升。这两种炎症性疾病都会导致呼吸急促，通常使用支气管扩张剂和糖皮质激素进行治疗，但效果不佳。这两种疾病的对症治疗方法相似；然而，潜在的免疫机制却大不相同。显然需要改善针对哮喘和 COPD 的治疗方法。本综述介绍了 TLRs 在哮喘和 COPD 中的作用，并讨论了将这些蛋白作为气道疾病新型治疗策略的优点和困难。TLR 激动剂、TLR 佐剂和 TLR 拮抗剂治疗都可能被认为对气道疾病的管理有效。由于 TLRs 在具有共同症状和危险因素但不同免疫机制的气道疾病中可能具有双重作用，在设计基于 TLR 的肺部治疗时应谨慎。
