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普利蒂素作为对抗呼吸道病毒感染的免疫调节剂

Alejandro Losada¹, Nuria Izquierdo-Useros^2,3,4, Pablo Aviles¹

¹Department of Research and Development, PharmaMar S.A., Colmenar Viejo, Madrid, Spain.

Journal of immunology (Baltimore, Md. : 1950)

|February 28, 2024

概括

在SARS-CoV-2和流感模型中,plitidepsin有效地降低了互白素-6 (IL-6) 分泌和炎症性细胞因子. 这种针对宿主的化合物显示出作为病毒感染的免疫调节疗法具有前途.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
药理学药理学是指药理学的学科.

背景情况:

普利蒂素表现出强大的抗SARS-CoV-2活性,并减少肺炎.
洲际素-6 (IL-6) 是一种关键的细胞因子,与急性呼吸困扰综合征 (ARDS) 有关.

研究的目的:

在各种体外和体外模型中研究平立素对IL-6分泌的影响.
探索plitidepsin的免疫调节机制,特别是它对NF-κB信号传递的影响.

主要方法:

在暴露于SARS-CoV-2的人类巨细胞中评估IL-6的减少.
研究了在Resiquimod刺激的THP1单细胞中的IL-6mRNA和蛋白质水平.
分析了NF-κB结合和p65酸化.
评估了SARS-CoV-2和H1N1感染小鼠的细胞因子水平,这些小鼠接受了plitidepsin治疗.

主要成果:

普利蒂素显著降低了SARS-CoV-2暴露的巨细胞和resiquimod刺激的单细胞中的IL-6.
普利蒂素降低了IL-6mRNA和蛋白质水平,并抑制了NF-κB调节的转录和p65酸化.
在体内研究表明,在感染的小鼠中减少了IL-6和其他益炎性细胞因子,这些小鼠接受了plitidepsin治疗.

结论:

普利蒂素通过减少IL-6和其他促炎细胞因子,显示出显著的免疫调节作用.
这些发现支持了plitidepsin作为病毒感染治疗剂的潜力,利用抗病毒和免疫调节性质.

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