Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome.
Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome.
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DOI：
10.3389/fphar.2021.650295
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发表时间：
2021
影响因子：
5.6
通讯作者：
Smith PA
中科院分区：
文献类型：
--
作者：
Huarte E;Peel MT;Verbist K;Fay BL;Bassett R;Albeituni S;Nichols KE;Smith PA
炎症过度综合征包括一组异质性疾病，其特征在于严重炎症、多器官功能障碍和潜在死亡。响应于抗原刺激（例如，SARS-CoV-2感染），过度活化的CD 8 + T细胞和巨噬细胞产生高水平的促炎细胞因子，如IFN-γ、TNF-α、IL-6和IL-12。与高炎症综合征有关的多种炎症介质利用Janus激酶-信号转导子和转录激活子（JAK-STAT）级联来传播其生物学功能。我们的研究结果表明，设计用于模拟临床相关JAK-STAT通路抑制的口服ruxolitinib给药显著降低了多种炎症模型中免疫过度激活的有害后果。与靶向单一细胞因子的单克隆抗体疗法相反，ruxolitinib可有效下调与高炎症状态有关的多种细胞因子的功能效应，而不会产生广泛的免疫抑制。
Hyperinflammatory syndromes comprise a heterogeneous group of disorders characterized by severe inflammation, multiple organ dysfunction, and potentially death. In response to antigenic stimulus (e.g., SARS-CoV-2 infection), overactivated CD8+ T-cells and macrophages produce high levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-6, and IL-12. Multiple inflammatory mediators implicated in hyperinflammatory syndromes utilize the Janus kinase–signal transducers and activators of transcription (JAK-STAT) cascade to propagate their biological function. Our findings demonstrate that oral ruxolitinib dosing designed to mimic clinically relevant JAK-STAT pathway inhibition significantly reduces the harmful consequences of immune overactivation in multiple hyperinflammatory models. In contrast to monoclonal antibody therapies targeting a single cytokine, ruxolitinib effectively downregulates the functional effect of multiple cytokines implicated in hyperinflammatory states, without broad immunosuppression.
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影响因子：
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作者：
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影响因子：
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