Pharmacological validation of a novel exopolysaccharide from Streptomyces sp. 139 to effectively inhibit cytokine storms
Zhuochen Zhuang,
Yu Chen,
Zhe Liu,
Yu Fu,
Fei Wang,
Liping Bai
Affiliations
Zhuochen Zhuang
NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
Yu Chen
NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; School of Basic Medicine and Forensic Medicine, Baotou Medical College, Baotou, 014040, Inner Mongolia, China
Zhe Liu
NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
Yu Fu
NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China
Fei Wang
The Affiliated Hospital, Inner Mongolia Medical University, 1 Tong Dao Street, Hohhot, 010050, Inner Mongolia, China
Liping Bai
NHC Key Laboratory of Biotechnology of Antibiotics, CAMS Key Laboratory of Synthetic Biology for Drug Innovation, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; State Key Laboratory of Desert and Oasis Ecology, Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, China; Corresponding author. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, 100050, 1 Tian Tan Xi Li, Beijing, 100050, China.
With the rapid development of immunotherapy in recent years, cytokine storm has been recognized as a common adverse effect of immunotherapy. The emergence of COVID-19 has renewed global attention to it. The cytokine storm's inflammatory response results in infiltration of large amounts of monocytes/macrophages in the lungs, heart, spleen, lymph nodes, and kidneys. This infiltration leads to secondary tissue damage, acute respiratory distress syndrome (ARDS), organismal damage, and even death. However, there is currently no designated treatment for cytokine storm and the resulting ARDS. Consequently, there is a pressing need to identify a pharmaceutical agent that can effectively mitigate cytokine storms. Ebosin is a new exopolysaccharide generated by Streptomyces sp.139 and pharmacological activity for cytokine storm is investigated in vivo. The results show that Ebosin significantly augments the survival rates of mice, and its effectiveness increases with higher doses. It significantly inhibited the expression of cytokines IL-5, IL-6, IL-9 and chemokine Eotaxin in serum and lung tissues. Ebosin can alleviate the pathological damage in the lungs, liver, and spleen caused by LPS. Additionally, it can inhibit the phosphorylation of IKKα/β, Stat3 and NF-κB p65 upon LPS stimulation in vitro. We hypothesized that Ebosin may decrease cytokine release by inhibiting the phosphorylation of IKKα/β, Stat3, and NF-κB p65, neutrophil infiltration in animals. The article preliminarily elucidated the activity and mechanism of Ebosin against cytokine storm, which provides a reference for the study of anti-cytokine storm activity of microbial natural products.
