Peter Angela E, Sandeep B V, Rao B Ganga, Kalpana V Lakshmi
Department of Biotechnology, College of Science and Technology, Andhra University, Visakhapatnam, India.
Andhra University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, India.
Front Pharmacol. 2021 Jan 27;11:583777. doi: 10.3389/fphar.2020.583777. eCollection 2020.
The COVID-19 pandemic has caused a global health crisis, with no specific antiviral to treat the infection and the absence of a suitable vaccine to prevent it. While some individuals contracting the SARS-CoV-2 infection exhibit a well coordinated immune response and recover, others display a dysfunctional immune response leading to serious complications including ARDS, sepsis, MOF; associated with morbidity and mortality. Studies revealed that in patients with a dysfunctional immune response, there is a massive cytokine and chemokine release, referred to as the 'cytokine storm'. As a result, such patients exhibit higher levels of pro-inflammatory/modulatory cytokines and chemokines like TNFα, INFγ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, MCSF, HGF and chemokines CXCL8, MCP1, IP10, MIP1α and MIP1β. Targeting this cytokine storm is a novel, promising treatment strategy to alleviate this excess influx of cytokines observed at the site of infection and their subsequent disastrous consequences. Natural immunosuppressant compounds, derived from plant sources like curcumin, luteolin, piperine, resveratrol are known to inhibit the production and release of pro-inflammatory cytokines and chemokines. This inhibitory effect is mediated by altering signal pathways like NF-κB, JAK/STAT, MAPK/ERK that are involved in the production and release of cytokines and chemokines. The use of these natural immunosuppressants as adjuvants to ameliorate the cytokine storm; in combination with antiviral agents and other treatment drugs currently in use presents a novel, synergistic approach for the treatment and effective cure of COVID-19. This review briefly describes the immunopathogenesis of the cytokine storm observed in SARS-CoV-2 infection and details some natural immunosuppressants that can be used as adjuvants in treating COVID-19 disease.
新冠疫情引发了一场全球健康危机，目前尚无特效抗病毒药物治疗该感染，也没有合适的疫苗预防感染。虽然一些感染新冠病毒的个体表现出协调良好的免疫反应并康复，但另一些人则表现出免疫反应功能失调，导致包括急性呼吸窘迫综合征（ARDS）、败血症、多器官功能衰竭（MOF）等严重并发症，与发病率和死亡率相关。研究表明，在免疫反应功能失调的患者中，会出现大量细胞因子和趋化因子释放，即所谓的“细胞因子风暴”。因此，这类患者表现出更高水平的促炎/调节性细胞因子和趋化因子，如肿瘤坏死因子α（TNFα）、干扰素γ（INFγ）、白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-7（IL-7）、白细胞介素-9（IL-9）、白细胞介素-10（IL-10）、白细胞介素-12（IL-12）、白细胞介素-13（IL-13）、白细胞介素-17（IL-17）、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、巨噬细胞集落刺激因子（MCSF）、肝细胞生长因子（HGF）以及趋化因子CXCL8、单核细胞趋化蛋白-1（MCP1）、干扰素诱导蛋白10（IP10）、巨噬细胞炎性蛋白-1α（MIP1α）和巨噬细胞炎性蛋白-1β（MIP1β）。针对这种细胞因子风暴是一种新颖且有前景的治疗策略，可缓解在感染部位观察到的细胞因子过度涌入及其后续灾难性后果。源自植物的天然免疫抑制化合物，如姜黄素、木犀草素、胡椒碱、白藜芦醇，已知可抑制促炎细胞因子和趋化因子的产生和释放。这种抑制作用是通过改变参与细胞因子和趋化因子产生和释放的信号通路，如核因子κB（NF-κB）、Janus激酶/信号转导子和转录激活子（JAK/STAT）、丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）来介导的。使用这些天然免疫抑制剂作为佐剂来改善细胞因子风暴；与目前使用的抗病毒药物和其他治疗药物联合使用，为新冠治疗和有效治愈提供了一种新颖的协同方法。本综述简要描述了在新冠病毒感染中观察到的细胞因子风暴的免疫发病机制，并详细介绍了一些可作为佐剂用于治疗新冠疾病的天然免疫抑制剂。
