Background

Neutrophilic inflammation, characterized by dysregulated neutrophil activation, triggers a variety of inflammatory responses such as chemotactic infiltration, oxidative bursts, degranulation, neutrophil extracellular traps (NETs) formation, and delayed turnover. This type of inflammation is pivotal in the pathogenesis of acute respiratory distress syndrome (ARDS) and psoriasis. Despite current treatments, managing neutrophil-associated inflammatory symptoms remains a significant challenge.

Aim of review:

This review emphasizes the role of cyclin-dependent kinases (CDKs) in neutrophil activation and inflammation. It aims to highlight the therapeutic potential of repurposing CDK inhibitors to manage neutrophilic inflammation, particularly in ARDS and psoriasis. Additionally, it discusses the necessary precautions for the clinical application of these inhibitors due to potential off-target effects and the need for dose optimization.

Key scientific concepts of review:

CDKs regulate key neutrophilic functions, including chemotactic responses, degranulation, NET formation, and apoptosis. Repurposing CDK inhibitors, originally developed for cancer treatment, shows promise in controlling neutrophilic inflammation. Clinical anticancer drugs, palbociclib and ribociclib, have demonstrated efficacy in treating neutrophilic ARDS and psoriasis by targeting off-label pathways, phosphoinositide 3-kinase (PI3K) and phosphodiesterase 4 (PDE4), respectively. While CDK inhibitors offer promising therapeutic benefits, their clinical repurposing requires careful consideration of off-target effects and dose optimization. Further exploration and clinical trials are necessary to ensure their safety and efficacy in treating inflammatory conditions.

中文翻译：

---

细胞周期蛋白依赖性激酶抑制剂治疗中性粒细胞急性呼吸窘迫综合征和银屑病的药物再利用

 背景

中性粒细胞炎症以中性粒细胞活化失调为特征，可触发多种炎症反应，如趋化浸润、氧化爆发、脱颗粒、中性粒细胞胞外陷阱 （NETs） 形成和延迟周转。这种类型的炎症在急性呼吸窘迫综合征 （ARDS） 和银屑病的发病机制中起着关键作用。尽管目前有治疗方法，但管理中性粒细胞相关的炎症症状仍然是一项重大挑战。

 综述目的：

本综述强调了细胞周期蛋白依赖性激酶 （CDK） 在中性粒细胞活化和炎症中的作用。它旨在强调再利用 CDK 抑制剂治疗中性粒细胞炎症的治疗潜力，尤其是在 ARDS 和银屑病中。此外，它还讨论了由于潜在的脱靶效应和剂量优化需求而导致这些抑制剂临床应用的必要预防措施。

综述的关键科学概念：

CDK 调节关键的嗜中性粒细胞功能，包括趋化反应、脱颗粒、NET 形成和细胞凋亡。重新利用最初为癌症治疗开发的 CDK 抑制剂在控制中性粒细胞炎症方面显示出前景。临床抗癌药物 palbociclib 和 ribociclib 已通过分别靶向标签外途径磷酸肌醇 3-激酶 （PI3K） 和磷酸二酯酶 4 （PDE4） 在治疗中性粒细胞性 ARDS 和银屑病方面显示出疗效。虽然 CDK 抑制剂提供了有希望的治疗益处，但其临床再利用需要仔细考虑脱靶效应和剂量优化。需要进一步的探索和临床试验，以确保它们在治疗炎症性疾病方面的安全性和有效性。