Emerging treatments for asthma.
Emerging treatments for asthma.
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DOI：
10.1517/eoed.8.1.71.21043
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Raymon, Heather K
中科院分区：
文献类型：
--
作者：
Blease, Kate;Lewis, Alan;Raymon, Heather K
尽管有大量的药物可用，哮喘的流行仍在继续增加。显然，仍然存在高度的、未得到满足的医疗需求，迫切需要创新的治疗剂。现有的治疗方法，如β-激动剂和皮质类固醇，为轻至中度哮喘患者提供了缓解，逆转了急性支气管收缩，减少了炎症。然而，这些疗法对慢性哮喘患者几乎没有缓解作用。哮喘是细胞因子和信号通路失衡的一种表现，这些通路介导了肺部的炎症和结构变化。需要开发新的疗法来针对这些变化。新出现的哮喘治疗方法包括改变细胞因子/趋化因子平衡的策略，使细胞因子谱偏离辅助性T细胞(Th)2反应，转向Th1反应。为此设计的策略包括针对IL-13、IL-4或它们的受体以及Th1细胞因子IL-12的治疗性抗体或小分子抑制剂。许多人的兴趣集中在哮喘所涉及的信号通路上。其中，有丝分裂原活化蛋白激酶(MAPK)途径成员c-jun氨基末端激酶(JNK)和p38，以及转录因子核因子-kappaB(NF-kappaB)、激活蛋白-1(AP-1)和信号转导与转录激活因子(STAT)-6引起了人们的广泛关注。本综述旨在总结慢性哮喘的新疗法，从早期发现到临床晚期，并讨论这些疗法背后的治疗原理。关于慢性哮喘的发展和治疗的机制仍有许多需要了解；然而，这些新疗法的未来前景很有希望。
Despite the availability of a great number of medications, the asthma epidemic is continuing to increase. It is obvious that a high, unmet medical need remains and innovative therapeutic agents are urgently required. Existing therapies, such as beta-agonists and corticosteroids, provide relief for sufferers of mild-to-moderate asthma, reversing the acute bronchoconstriction and decreasing the inflammation. However, these therapies provide little relief for chronic asthmatics. Asthma is a manifestation of an imbalance in cytokine and signalling pathways that mediate inflammatory and structural changes within the lung. New therapies need to be developed to target these changes. Emerging treatments for asthma include strategies to alter the cytokine/chemokine balance, to skew the cytokine profile away from a T helper (Th)2 response and towards a Th1 response. Strategies designed to do this include therapeutic antibodies or small molecule inhibitors targeted towards IL-13, IL-4 or their receptors, and the Th1 cytokine IL-12. Much interest has focused on the signalling pathways involved in asthma. Among these, the mitogen-activated protein kinase (MAPK) pathway members c-Jun N-terminal kinase (JNK) and p38 have gathered much interest, in addition to the transcription factors nuclear factor kappaB (NF-kappa B), activator protein-1 (AP-1) and signal transducer and activator of transcription (STAT)-6. This review aims to summarise the emerging treatments for chronic asthma, from early discovery, to late clinical stages, and discuss the therapeutic rationale behind these treatments. Much is still to be learned about the mechanisms involved in the development and treatment of chronic asthma; however, much promise lies in the future of these new therapeutics.