Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm
Excessive inflammation associated with the uncontrolled release of pro-inflammatory cytokines is the main cause of death from influenza virus infection. Previous studies have indicated that inhibition of interferon gamma-induced protein 10 (IP-10), interleukin-8 (IL-8), monocyte chemoattractant prot...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01393/full |
| _version_ | 1818048379354087424 |
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| author | Si Chen Si Chen Ge Liu Ge Liu Jungang Chen Ao Hu Ao Hu Li Zhang Li Zhang Wenyu Sun Wenyu Sun Wei Tang Chunlan Liu Haiwei Zhang Chang Ke Jianguo Wu Xulin Chen Xulin Chen |
| author_facet | Si Chen Si Chen Ge Liu Ge Liu Jungang Chen Ao Hu Ao Hu Li Zhang Li Zhang Wenyu Sun Wenyu Sun Wei Tang Chunlan Liu Haiwei Zhang Chang Ke Jianguo Wu Xulin Chen Xulin Chen |
| author_sort | Si Chen |
| collection | DOAJ |
| description | Excessive inflammation associated with the uncontrolled release of pro-inflammatory cytokines is the main cause of death from influenza virus infection. Previous studies have indicated that inhibition of interferon gamma-induced protein 10 (IP-10), interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), or their cognate receptors has beneficial effects. Here, by using monocytic U937 cells that capable of secreting the three important cytokines during influenza A virus infection, we measured the inhibitory activities on the production of three cytokines of six anti-inflammatory compounds reported in other models of inflammation. We found that ponatinib had a highly inhibitory effect on the production of all three cytokines. We tested ponatinib in a mouse influenza model to assess its therapeutic effects with different doses and administration times and found that the delayed administration of ponatinib was protective against lethal influenza A virus infection without reducing virus titers. Therefore, we suggest that ponatinib may serve as a new immunomodulator in the treatment of influenza. |
| first_indexed | 2024-12-10T10:20:45Z |
| format | Article |
| id | doaj.art-f3d97d16e80248d0abbd53681dacfe1e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T10:20:45Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f3d97d16e80248d0abbd53681dacfe1e2022-12-22T01:52:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01393451302Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine StormSi Chen0Si Chen1Ge Liu2Ge Liu3Jungang Chen4Ao Hu5Ao Hu6Li Zhang7Li Zhang8Wenyu Sun9Wenyu Sun10Wei Tang11Chunlan Liu12Haiwei Zhang13Chang Ke14Jianguo Wu15Xulin Chen16Xulin Chen17State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaWuhan Virolead Biopharmaceutical Company, Wuhan, ChinaGuangzhou Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, ChinaState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaExcessive inflammation associated with the uncontrolled release of pro-inflammatory cytokines is the main cause of death from influenza virus infection. Previous studies have indicated that inhibition of interferon gamma-induced protein 10 (IP-10), interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), or their cognate receptors has beneficial effects. Here, by using monocytic U937 cells that capable of secreting the three important cytokines during influenza A virus infection, we measured the inhibitory activities on the production of three cytokines of six anti-inflammatory compounds reported in other models of inflammation. We found that ponatinib had a highly inhibitory effect on the production of all three cytokines. We tested ponatinib in a mouse influenza model to assess its therapeutic effects with different doses and administration times and found that the delayed administration of ponatinib was protective against lethal influenza A virus infection without reducing virus titers. Therefore, we suggest that ponatinib may serve as a new immunomodulator in the treatment of influenza.https://www.frontiersin.org/article/10.3389/fimmu.2019.01393/fullcytokine stormimmunomodulatorinfluenza A virusponatinibpro-inflammatory cytokine |
| spellingShingle | Si Chen Si Chen Ge Liu Ge Liu Jungang Chen Ao Hu Ao Hu Li Zhang Li Zhang Wenyu Sun Wenyu Sun Wei Tang Chunlan Liu Haiwei Zhang Chang Ke Jianguo Wu Xulin Chen Xulin Chen Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm Frontiers in Immunology cytokine storm immunomodulator influenza A virus ponatinib pro-inflammatory cytokine |
| title | Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm |
| title_full | Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm |
| title_fullStr | Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm |
| title_full_unstemmed | Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm |
| title_short | Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm |
| title_sort | ponatinib protects mice from lethal influenza infection by suppressing cytokine storm |
| topic | cytokine storm immunomodulator influenza A virus ponatinib pro-inflammatory cytokine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01393/full |
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