Deep insight into cytokine storm: from pathogenesis to treatment
Abstract Cytokine storm (CS) is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines. This pathological process is implicated in the development of life-threatening conditions such as fulminant...
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| Format: | Article |
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Nature Publishing Group
2025-04-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02178-y |
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| author | Jiali Nie Ling Zhou Weiwei Tian Xiansheng Liu Liping Yang Xingcheng Yang Yicheng Zhang Shuang Wei Dao Wen Wang Jia Wei |
| author_facet | Jiali Nie Ling Zhou Weiwei Tian Xiansheng Liu Liping Yang Xingcheng Yang Yicheng Zhang Shuang Wei Dao Wen Wang Jia Wei |
| author_sort | Jiali Nie |
| collection | DOAJ |
| description | Abstract Cytokine storm (CS) is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines. This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis (FM), acute respiratory distress syndrome (ARDS), primary or secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome (CRS) associated with chimeric antigen receptor-modified T (CAR-T) therapy, and grade III to IV acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. The significant involvement of the JAK-STAT pathway, Toll-like receptors, neutrophil extracellular traps, NLRP3 inflammasome, and other signaling pathways has been recognized in the pathogenesis of CS. Therapies targeting these pathways have been developed or are currently being investigated. While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS, the overall mortality rate of CS resulting from underlying diseases remains high. In the clinical setting, the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation, the preservation of vital organ function, the treatment of the underlying disease, and the provision of life supportive therapy. This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS, elucidates the impact of dysregulated immune cell activation, and delineates the resultant organ injury associated with CS. In addition, we offer insights and current literature on the management of CS in cases of FM, ARDS, systemic inflammatory response syndrome, treatment-induced CRS, HLH, and other related conditions. |
| format | Article |
| id | doaj-art-84199f4bb20f468baf5f69aece892c75 |
| institution | DOAJ |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-84199f4bb20f468baf5f69aece892c752025-08-20T03:18:23ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-04-0110113810.1038/s41392-025-02178-yDeep insight into cytokine storm: from pathogenesis to treatmentJiali Nie0Ling Zhou1Weiwei Tian2Xiansheng Liu3Liping Yang4Xingcheng Yang5Yicheng Zhang6Shuang Wei7Dao Wen Wang8Jia Wei9Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory and Critical Care Medicine, National Health Commission (NHC) Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, National Health Commission (NHC) Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical UniversityDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Respiratory and Critical Care Medicine, National Health Commission (NHC) Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Cytokine storm (CS) is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines. This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis (FM), acute respiratory distress syndrome (ARDS), primary or secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome (CRS) associated with chimeric antigen receptor-modified T (CAR-T) therapy, and grade III to IV acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. The significant involvement of the JAK-STAT pathway, Toll-like receptors, neutrophil extracellular traps, NLRP3 inflammasome, and other signaling pathways has been recognized in the pathogenesis of CS. Therapies targeting these pathways have been developed or are currently being investigated. While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS, the overall mortality rate of CS resulting from underlying diseases remains high. In the clinical setting, the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation, the preservation of vital organ function, the treatment of the underlying disease, and the provision of life supportive therapy. This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS, elucidates the impact of dysregulated immune cell activation, and delineates the resultant organ injury associated with CS. In addition, we offer insights and current literature on the management of CS in cases of FM, ARDS, systemic inflammatory response syndrome, treatment-induced CRS, HLH, and other related conditions.https://doi.org/10.1038/s41392-025-02178-y |
| spellingShingle | Jiali Nie Ling Zhou Weiwei Tian Xiansheng Liu Liping Yang Xingcheng Yang Yicheng Zhang Shuang Wei Dao Wen Wang Jia Wei Deep insight into cytokine storm: from pathogenesis to treatment Signal Transduction and Targeted Therapy |
| title | Deep insight into cytokine storm: from pathogenesis to treatment |
| title_full | Deep insight into cytokine storm: from pathogenesis to treatment |
| title_fullStr | Deep insight into cytokine storm: from pathogenesis to treatment |
| title_full_unstemmed | Deep insight into cytokine storm: from pathogenesis to treatment |
| title_short | Deep insight into cytokine storm: from pathogenesis to treatment |
| title_sort | deep insight into cytokine storm from pathogenesis to treatment |
| url | https://doi.org/10.1038/s41392-025-02178-y |
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