Viral-Immunobiology Laboratory, Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Virology. 2013 Jan 5;435(1):92-101. doi: 10.1016/j.virol.2012.09.039.
The cytokine storm is an aggressive immune response characterized by the recruitment of inflammatory leukocytes and exaggerated levels of cytokines and chemokines at the site of infection. Here we review evidence that cytokine storm directly contributes to the morbidity and mortality resulting from influenza virus infection and that sphingosine-1-phosphate (S1P) receptor agonists can abort cytokine storms providing significant protection against pathogenic human influenza viral infections. In experiments using murine models and the human pathogenic 2009 influenza viruses, S1P1 receptor agonist alone reduced deaths from influenza virus by over 80% as compared to lesser protection (50%) offered by the antiviral neuraminidase inhibitor oseltamivir. Optimal protection of 96% was achieved by combined therapy with the S1P1 receptor agonist and oseltamivir. The functional mechanism of S1P receptor agonist(s) action and the predominant role played by pulmonary endothelial cells as amplifiers of cytokine storm during influenza infection are described.
细胞因子风暴是一种侵袭性免疫反应，其特征是在感染部位招募炎症性白细胞，并伴有细胞因子和趋化因子的过度水平。在这里，我们回顾了细胞因子风暴直接导致流感病毒感染的发病率和死亡率的证据，并且发现鞘氨醇-1-磷酸（S1P）受体激动剂可以中止细胞因子风暴，对致病性人流感病毒感染提供显著保护。在使用鼠模型和人类致病性 2009 流感病毒的实验中，与抗病毒神经氨酸酶抑制剂奥司他韦提供的较小保护（50%）相比，S1P1 受体激动剂单独使用将流感病毒引起的死亡率降低了 80%以上。S1P1 受体激动剂和奥司他韦联合治疗可实现 96%的最佳保护。描述了 S1P 受体激动剂作用的功能机制以及在流感感染期间肺内皮细胞作为细胞因子风暴放大器所起的主要作用。
