Abstract
It has become evident that the actions of pro-inflammatory cytokines and/or the development of a cytokine storm are responsible for the occurrence of severe COVID-19 during SARS-CoV-2 infection. Although immunomodulatory mechanisms vary among viruses, the activation of multiple TLRs that occurs primarily through the recruitment of adapter proteins such as MyD88 and TRIF contributes to the induction of a cytokine storm. Based on this, controlling the robust production of pro-inflammatory cytokines by macrophages may be applicable as a cellular approach to investigate potential cytokine-targeted therapies against COVID-19. In the current study, we utilized TLR2/MyD88 and TLR3/TRIF co-activated macrophages and evaluated the anti-cytokine storm effect of the traditional Chinese medicine (TCM) formula Babaodan (BBD). An RNA-seq-based transcriptomic approach was used to determine the molecular mode of action. Additionally, we evaluated the anti-inflammatory activity of BBD in vivo using a mouse model of post-viral bacterial infection-induced pneumonia and seven severely ill COVID-19 patients. Our study reveals the protective role of BBD against excessive immune responses in macrophages, where the underlying mechanisms involve the inhibition of the NF-κB and MAPK signaling pathways. In vivo, BBD significantly inhibited the release of IL-6, thus resulting in increased survival rates in mice. Based on limited data, we demonstrated that severely ill COVID-19 patients benefited from BBD treatment due to a reduction in the overproduction of IL-6. In conclusion, our study indicated that BBD controls excessive immune responses and may thus represent a cytokine-targeted agent that could be considered to treating COVID-19.
Keywords: Babaodan; COVID-19; Cytokine storm; Inflammation; Traditional Chinese medicine.
【저자키워드】 COVID-19, Inflammation, Cytokine storm, Traditional Chinese medicine, Babaodan, 【초록키워드】 Treatment, viruses, Macrophage, Cytokine storm, therapy, Cytokines, macrophages, severe COVID-19, Pneumonia, IL-6, SARS-COV-2 infection, Traditional Chinese medicine, TLRs, anti-inflammatory activity, Protein, mice, immune responses, immunomodulatory, Control, Bacterial infection, pro-inflammatory cytokines, molecular, recruitment, in vivo, mouse model, mechanism, COVID-19 patients, NF-κB, Bacterial, TLR3, cellular, TCM, MAPK, Pathways, COVID-19 patient, Activation, TRIF, increased survival, Chinese, protective role, pro-inflammatory cytokine, severely ill COVID-19 patients, overproduction, TLR2, treating COVID-19, MAPK signaling, excessive immune response, adapter, MYD88, transcriptomic, TLR, approach, anti-cytokine storm, robust, Seven, Occurrence, responsible, resulting, was used, significantly, indicated, evaluated, inhibited, determine, contribute, occur, demonstrated, reveal, reduction in, 【제목키워드】 Treatment, Control, excessive immune response,