A review of Janus kinase inhibitors for the treatment of Covid-19 pneumonia.

IF 5 3区 医学 Q2 IMMUNOLOGY Inflammation and Regeneration Pub Date : 2023-01-09 DOI:10.1186/s41232-022-00253-3
Yoshiya Tanaka
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引用次数: 6

Abstract

Background: In inflamed tissue, immune cells are accumulated, and various intercellular signals are involved in the pathogenesis. Janus kinases (JAKs) are typical tyrosine kinases involved in mediating the signaling of multiple cytokines and growth factors and induce the transcription of molecules related to inflammation or immunity via the transcription factor signal transducers and activators of transcription (STAT). Hence, they have garnered significant interest as a therapeutic target. JAK inhibitors have been evaluated as a major drug for remission induction in the treatment of autoimmune diseases such as rheumatoid arthritis. BODY: Covid-19 infection due to SARS-CoV-2 has caused a pandemic, with approximately 660 million infections and 6.7 million deaths worldwide (January, 2023). The prognosis is poor and the major causes of death are respiratory failure attributed to rapid pneumonia, thromboembolism due to a cytokine storm, and multi-organ failure. As a treatment modality, molecular targeted therapy, such as cytokine-targeting therapy, is attracting attention, in addition to antiviral drugs. Baricitinib, a JAK inhibitor, is used for the treatment of severe pneumonia, in addition to antiviral drugs and glucocorticoids. The mechanism of action of baricitinib includes inhibition of viral receptor-mediated endocytosis, which involves the NF-κB activating kinase (NAK) family, and mediating the anti-cytokine effects via JAK 1/2 inhibition. It improves severe pneumonia and reduces mortality.

Conclusion: Thus, the development of molecular targeted drugs with elucidated pathological mechanisms may aid in controlling Covid-19 infection.

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Janus激酶抑制剂治疗Covid-19肺炎的研究进展
背景:炎症组织中免疫细胞聚集,多种细胞间信号参与其发病。Janus激酶(JAKs)是典型的酪氨酸激酶,参与介导多种细胞因子和生长因子的信号转导,并通过转录因子信号转导和转录激活因子(STAT)诱导炎症或免疫相关分子的转录。因此,它们作为一种治疗靶点引起了人们极大的兴趣。JAK抑制剂已被评估为治疗自身免疫性疾病(如类风湿关节炎)缓解诱导的主要药物。由SARS-CoV-2引起的Covid-19感染已引起大流行,全球约有6.6亿人感染,670万人死亡(2023年1月)。预后很差,死亡的主要原因是快速肺炎引起的呼吸衰竭、细胞因子风暴引起的血栓栓塞和多器官衰竭。除抗病毒药物外,分子靶向治疗(如细胞因子靶向治疗)作为一种治疗方式正在引起人们的关注。Baricitinib是一种JAK抑制剂,除抗病毒药物和糖皮质激素外,还用于治疗严重肺炎。巴比替尼的作用机制包括抑制病毒受体介导的内吞作用,其中涉及NF-κB活化激酶(NAK)家族,并通过抑制JAK 1/2介导抗细胞因子作用。它可以改善严重肺炎并降低死亡率。结论:开发病理机制明确的分子靶向药物可能有助于控制新冠病毒感染。
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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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