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趋化因子和趋化因子受体阻滞剂作为治疗慢性阻塞性肺疾病的新药。

Chemokines and chemokine receptors blockers as new drugs for the treatment of chronic obstructive pulmonary disease.

机构信息

Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumocorrelate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Università di Ferrara Via Savonarola 9 44121 Ferrara, Italy.

出版信息

Curr Med Chem. 2013;20(35):4317-49. doi: 10.2174/09298673113206660261.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response of the lung to noxious particles or gases. The cellular inflammatory response in COPD is characterised by an increased number of inflammatory cells in the lungs. Although the molecular and cellular mechanisms responsible for the development of COPD are not well understood; several mediators are assumed to regulate the activation and recruitment of these inflammatory cells into the lung of COPD patients particularly those belonging to the chemokine family. Inhibitors or blockers of chemokine and chemokine receptors are therefore of great interest as potential novel therapies for COPD and many are now in clinical development. A high degree of redundancy exists in the chemokine network and inhibition of a single chemokine or receptor may not be sufficient to block the inflammatory response. Despite this, animal studies suggest a strong rationale for inhibiting the chemokine network in COPD. As such, every leading pharmaceutical company maintains a significant interest in developing agents that regulate leukocyte navigation as potential anti-inflammatory drugs. Drugs and antibodies targeting chemokines and their receptors are generally still in early stages of development and the results of clinical trial are awaited with great interest. These agents may not only provide improved management of COPD but also, importantly, indicate proof-of-concept to further clarify the role of chemokines in the pathophysiology of COPD.

摘要

慢性阻塞性肺疾病(COPD)的特征是肺对有害颗粒或气体的异常炎症反应。COPD 中的细胞炎症反应的特征是肺部炎症细胞数量增加。尽管导致 COPD 发展的分子和细胞机制尚不清楚;但有几种介质被认为可以调节这些炎症细胞向 COPD 患者肺部的激活和募集,特别是那些属于趋化因子家族的介质。因此,趋化因子及其受体的抑制剂或阻滞剂作为 COPD 的潜在新型治疗方法具有重要意义,许多药物现在正在临床开发中。趋化因子网络中存在高度冗余,抑制单一趋化因子或受体可能不足以阻断炎症反应。尽管如此,动物研究表明抑制 COPD 中的趋化因子网络具有很强的理论依据。因此,每家领先的制药公司都对开发调节白细胞导航的药物作为潜在的抗炎药物保持着浓厚的兴趣。针对趋化因子及其受体的药物和抗体通常仍处于早期开发阶段,人们非常关注临床试验的结果。这些药物不仅可以改善 COPD 的管理,而且重要的是,为进一步阐明趋化因子在 COPD 病理生理学中的作用提供了概念验证。

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