Treating exuberant, non-resolving inflammation in the lung; Implications for acute respiratory distress syndrome and COVID-19.
Treating exuberant, non-resolving inflammation in the lung; Implications for acute respiratory distress syndrome and COVID-19.
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DOI：
10.1016/j.pharmthera.2020.107745
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发表时间：
2021-05
影响因子：
13.5
通讯作者：
Akbar AN
中科院分区：
文献类型：
--
作者：
Gilroy DW;De Maeyer RPH;Tepper M;O'Brien A;Uddin M;Chen J;Goldstein DR;Akbar AN
虽然由 SARS-CoV-2 驱动的疾病 COVID-19 引发了人们对宿主对这种感染的免疫反应的兴趣，但它也突显了对于由诱发急性呼吸窘迫综合征 (ARDS) 的病原体驱动的破坏性炎症反应缺乏治疗选择。随着 SARS-CoV-2 在全球的流行，以及季节性流感可能出现第二次冬季高峰，对有效且有针对性的抗炎药物的需求更加迫切。在这里，我们讨论了 COVID-19 的病因学以及 SARS-CoV-2 驱动的常见信号通路，即 p38 MAP 激酶。我们强调，p38 MAP 激酶随着年龄的增长而升高，从而驱动许多导致老年人死亡的炎症途径，并带来损害该易感年龄组疫苗功效的额外缺点。最后，我们回顾了可用于抑制 p38 MAP 激酶的药物、它们的风险与益处以及建议的剂量方案，以对抗过度旺盛的先天免疫反应，并可能逆转老年患者的疫苗无效。
While COVID-19, the disease driven by SARS-CoV-2 has ignited interest in the host immune response to this infection, it has also highlighted the lack of treatment options for the damaging inflammatory responses driven by pathogens that precipitate the acute respiratory distress syndrome (ARDS). With the global prevalence of SARS-CoV-2 and the likelihood of a second winter spike alongside seasonal flu, the need for effective and targeted anti-inflammatory agents is even more pressing. Here we discuss the aetiology of COVID-19 and the common signalling pathways driven by SARS-CoV-2, namely p38 MAP kinase. We highlight that p38 MAP kinase becomes elevated with increasing age, thereby driving many of the inflammatory pathways that precipitate death in old people with the added drawback of impairing vaccine efficacy in this susceptible age group. Finally, we review drugs available to inhibit p38 MAP kinase, their risks-versus-benefits as well as suggested dosing regimen to combat over-exuberant innate immune responses and potentially reverse vaccine inefficacy in older patients.
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DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan
影响因子：
3
作者：
Fisk, Marie;Gajendragadkar, Parag R.;Cheriyan, Joseph
通讯作者：
Cheriyan, Joseph
影响因子：
64.5
作者：
Bouhaddou, Mehdi;Memon, Danish;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.
影响因子：
3.7
作者：
Fisk M;Cheriyan J;Mohan D;Forman J;Mäki-Petäjä KM;McEniery CM;Fuld J;Rudd JHF;Hopkinson NS;Lomas DA;Cockcroft JR;Tal-Singer R;Polkey MI;Wilkinson IB
通讯作者：
Wilkinson IB