Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities.
Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities.
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DOI：
10.1016/s2213-2600(20)30267-8
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Chambers RC
中科院分区：
文献类型：
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作者：
Mehta P;Porter JC;Manson JJ;Isaacs JD;Openshaw PJM;McInnes IB;Summers C;Chambers RC
COVID-19大流行是一场全球公共卫生危机，相当高的死亡率和发病率对医疗资源（包括重症护理）造成压力。严重COVID-19患者亚组的过度宿主炎症反应可能导致急性呼吸窘迫综合征（ARDS）和多器官衰竭的发生。对高炎症患者及时进行免疫调节治疗干预可以防止疾病进展为ARDS，并减少有创通气的需要。粒细胞巨噬细胞集落刺激因子（GM-CSF）是一种免疫调节细胞因子，在炎症性疾病的发生和发展中起着重要作用。GM-CSF可将T细胞驱动的急性肺部炎症与导致单核细胞和巨噬细胞活化的自分泌、自我放大的细胞因子环联系起来。该轴已在细胞因子风暴综合征和慢性炎症性疾病中被靶向。在这里，我们考虑了GM-CSF治疗COVID-19相关炎症过度的科学依据。由于GM-CSF在体内平衡和宿主防御中也具有关键作用，因此我们讨论了在病毒感染的背景下与GM-CSF抑制相关的潜在风险以及在这种情况下进行临床试验的挑战，特别强调了对患者风险分层算法的需求。
The COVID-19 pandemic is a global public health crisis, with considerable mortality and morbidity exerting pressure on health-care resources, including critical care. An excessive host inflammatory response in a subgroup of patients with severe COVID-19 might contribute to the development of acute respiratory distress syndrome (ARDS) and multiorgan failure. Timely therapeutic intervention with immunomodulation in patients with hyperinflammation could prevent disease progression to ARDS and obviate the need for invasive ventilation. Granulocyte macrophage colony-stimulating factor (GM-CSF) is an immunoregulatory cytokine with a pivotal role in initiation and perpetuation of inflammatory diseases. GM-CSF could link T-cell-driven acute pulmonary inflammation with an autocrine, self-amplifying cytokine loop leading to monocyte and macrophage activation. This axis has been targeted in cytokine storm syndromes and chronic inflammatory disorders. Here, we consider the scientific rationale for therapeutic targeting of GM-CSF in COVID-19-associated hyperinflammation. Since GM-CSF also has a key role in homoeostasis and host defence, we discuss potential risks associated with inhibition of GM-CSF in the context of viral infection and the challenges of doing clinical trials in this setting, highlighting in particular the need for a patient risk-stratification algorithm.