Recent progress and prospects for anti-cytokine therapy in preclinical and clinical acute lung injury

IF 9.3 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Guilherme Pasetto Fadanni , João Batista Calixto
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引用次数: 0

Abstract

Acute respiratory distress syndrome (ARDS) is a heterogeneous cause of respiratory failure that has a rapid onset, a high mortality rate, and for which there is no effective pharmacological treatment. Current evidence supports a critical role of excessive inflammation in ARDS, resulting in several cytokines, cytokine receptors, and proteins within their downstream signalling pathways being putative therapeutic targets. However, unsuccessful trials of anti-inflammatory drugs have thus far hindered progress in the field. In recent years, the prospects of precision medicine and therapeutic targeting of cytokines coevolving into effective treatments have gained notoriety. There is an optimistic and growing understanding of ARDS subphenotypes as well as advances in treatment strategies and clinical trial design. Furthermore, large trials of anti-cytokine drugs in patients with COVID-19 have provided an unprecedented amount of information that could pave the way for therapeutic breakthroughs. While current clinical and nonclinical ARDS research suggest relatively limited potential in monotherapy with anti-cytokine drugs, combination therapy has emerged as an appealing strategy and may provide new perspectives on finding safe and effective treatments. Accurate evaluation of these drugs, however, also relies on well-founded experimental research and the implementation of biomarker-guided stratification in future trials. In this review, we provide an overview of anti-cytokine therapy for acute lung injury and ARDS, highlighting the current preclinical and clinical evidence for targeting the main cytokines individually and the therapeutic prospects for combination therapy.

Abstract Image

抗细胞因子治疗临床前和临床急性肺损伤的研究进展及展望
急性呼吸窘迫综合征(ARDS)是呼吸衰竭的一种异质性原因,发病迅速,死亡率高,而且没有有效的药物治疗。目前的证据支持过度炎症在ARDS中的关键作用,导致几种细胞因子、细胞因子受体及其下游信号通路中的蛋白质成为公认的治疗靶点。然而,迄今为止,抗炎药试验的失败阻碍了该领域的进展。近年来,精准医学和细胞因子靶向治疗共同转化为有效治疗的前景已经臭名昭著。人们对ARDS亚表型以及治疗策略和临床试验设计的进展有着乐观和不断增长的理解。此外,抗细胞因子药物在新冠肺炎患者中的大型试验提供了前所未有的信息,可能为治疗突破铺平道路。虽然目前的临床和非临床ARDS研究表明,抗细胞因子药物单药治疗的潜力相对有限,但联合治疗已成为一种有吸引力的策略,并可能为寻找安全有效的治疗方法提供新的视角。然而,对这些药物的准确评估也依赖于有充分依据的实验研究和在未来试验中实施生物标志物引导的分层。在这篇综述中,我们概述了抗细胞因子治疗急性肺损伤和ARDS的概况,强调了目前单独靶向主要细胞因子的临床前和临床证据,以及联合治疗的治疗前景。
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来源期刊
Cytokine & Growth Factor Reviews
Cytokine & Growth Factor Reviews 生物-生化与分子生物学
CiteScore
21.10
自引率
1.50%
发文量
61
审稿时长
22 days
期刊介绍: Cytokine & Growth Factor Reviews is a leading publication that focuses on the dynamic fields of growth factor and cytokine research. Our journal offers a platform for authors to disseminate thought-provoking articles such as critical reviews, state-of-the-art reviews, letters to the editor, and meeting reviews. We aim to cover important breakthroughs in these rapidly evolving areas, providing valuable insights into the multidisciplinary significance of cytokines and growth factors. Our journal spans various domains including signal transduction, cell growth and differentiation, embryonic development, immunology, tumorigenesis, and clinical medicine. By publishing cutting-edge research and analysis, we aim to influence the way researchers and experts perceive and understand growth factors and cytokines. We encourage novel expressions of ideas and innovative approaches to organizing content, fostering a stimulating environment for knowledge exchange and scientific advancement.
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