Leptin correlates with monocytes activation and severe condition in COVID-19 patients
Leptin correlates with monocytes activation and severe condition in COVID-19 patients
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瘦素与 COVID-19 患者的单核细胞活化和严重状况相关
DOI：
10.1002/jlb.5hi1020-704r
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发表时间：
2021-01-06
影响因子：
5.5
通讯作者：
Liu, Zhiqiang
中科院分区：
文献类型：
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作者：
Wang, Jingya;Xu, Yinyin;Liu, Zhiqiang
在2019年新型冠状病毒引起的肺炎患者中，单核细胞过度激活，伴随着致炎细胞因子的过度或不受控制的释放，往往会导致宿主组织损伤，甚至死亡。然而，冠状病毒病2019(新冠肺炎)患者细胞因子谱的变化以及涉及的潜在机制尚不清楚。利用包含炎症相关细胞因子的细胞因子阵列，我们发现重度新冠肺炎患者与轻度患者和健康对照组相比，细胞因子谱明显改变，并确定瘦素、CXCL-10、IL-6、IL-10、IL-12和肿瘤坏死因子-α是最显著的差异表达细胞因子。值得注意的是，瘦素与CxCL-10和肿瘤坏死因子-α在预测疾病严重程度方面表现出高度的一致性，并与体重指数、淋巴细胞计数下降和疾病进展相关。进一步分析表明，瘦素水平较高的重症患者单核细胞倾向于M1极化。机制研究表明，瘦素通过STAT3和NF-κB信号通路协同上调单核细胞中炎性细胞因子和表面标志与IL-6的表达水平。综上所述，我们的结果表明，超重的新冠肺炎患者容易有更高的瘦素水平，从而进一步激活单核细胞，导致放大或调节失调的免疫反应。综上所述，我们的发现认为，瘦素与新冠肺炎的严重程度相关，并可能表明一种可能的机制，通过这种机制，超重患者更有可能发展为严重疾病。
Excessive monocyte activation with the development of excessive or uncontrolled release of proinflammatory cytokines often results in host tissue injury and even death in patients with pneumonia caused by the 2019 novel coronavirus. However, the changes of cytokine profiles of coronavirus disease 2019 (COVID‐19) patients, as well as the underlying mechanisms that are involved, remain unknown. Using a cytokine array containing 174 inflammation‐related cytokines, we found significantly altered cytokine profiles in severe COVID‐19 patients compared with those in mild patients or healthy controls, and identified leptin, CXCL‐10, IL‐6, IL‐10, IL‐12, and TNF‐α as the top differentially expressed cytokines. Notably, leptin showed high consistency with CXCL‐10 and TNF‐α in predicting disease severity, and correlated with body mass index, decreased lymphocyte counts, and disease progression. Further analysis demonstrated that monocytes in severe patients with higher leptin levels were inclined toward M1 polarization. Mechanistic studies revealed that leptin synergistically up‐regulated expression levels of inflammatory cytokines and surface markers with IL‐6 in monocytes through STAT3 and NF‐κB signaling pathways. Collectively, our results suggest that overweight COVID‐19 patients were prone to have higher leptin levels, which further activated monocytes, resulting in amplified or dysregulated immune responses. Taken together, our findings argue that leptin correlates severity of COVID‐19 and may indicate a possible mechanism by which overweight patients have a greater tendency to develop severe conditions.