AMG487 alleviates influenza A (H1N1) virus-induced pulmonary inflammation through decreasing IFN-γ-producing lymphocytes and IFN-γ concentrations
© 2024 British Pharmacological Society..
BACKGROUND AND PURPOSE: Severe influenza virus-infected patients have high systemic levels of Th1 cytokines (including IFN-γ). Intrapulmonary IFN-γ increases pulmonary IFN-γ-producing T lymphocytes through the CXCR3 pathway. Virus-infected mice lacking IP-10/CXCR3 demonstrate lower pulmonary neutrophilic inflammation. AMG487, an IP-10/CXCR3 antagonist, ameliorates virus-induced lung injury in vivo through decreasing viral loads. This study examined whether AMG487 could treat H1N1 virus-induced mouse illness through reducing viral loads or decreasing the number of lymphocytes or neutrophils.
EXPERIMENTAL APPROACH: Here, we studied the above-mentioned effects and underlying mechanisms in vivo.
KEY RESULTS: H1N1 virus infection caused bad overall condition and pulmonary inflammation characterized by the infiltration of lymphocytes and neutrophils. From Day-5 to Day-10 post-virus infection, bad overall condition, pulmonary lymphocytes, and IFN-γ concentrations increased, while pulmonary H1N1 viral titres and neutrophils decreased. Both anti-IFN-γ and AMG487 alleviated virus infection-induced bad overall condition and pulmonary lymphocytic inflammation. Pulmonary neutrophilic inflammation was mitigated by AMG487 on Day-5 post-infection, but was not mitigated by AMG487 on Day-10 post-infection. H1N1 virus induced increases of IFN-γ, IP-10, and IFN-γ-producing lymphocytes and activation of the Jak2-Stat1 pathways in mouse lungs, which were inhibited by AMG487. Anti-IFN-γ decreased IFN-γ and IFN-γ-producing lymphocytes on Day-5 post-infection. AMG487 but not anti-IFN-γ decreased viral titres in mouse lung homogenates or BALF. Higher virus load did not increase pulmonary inflammation and IFN-γ concentrations when mice were treated with AMG487.
CONCLUSION AND IMPLICATIONS: AMG487 may ameliorate H1N1 virus-induced pulmonary inflammation through decreasing IFN-γ-producing lymphocytes rather than reducing viral loads or neutrophils.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
British journal of pharmacology - (2024) vom: 18. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ding, Wenbin [VerfasserIn] |
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| Links: |
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| Themen: |
AMG487 |
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| Anmerkungen: |
Date Revised 19.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/bph.16343 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369900383 |
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| 245 | 1 | 0 | |a AMG487 alleviates influenza A (H1N1) virus-induced pulmonary inflammation through decreasing IFN-γ-producing lymphocytes and IFN-γ concentrations |
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| 520 | |a © 2024 British Pharmacological Society. | ||
| 520 | |a BACKGROUND AND PURPOSE: Severe influenza virus-infected patients have high systemic levels of Th1 cytokines (including IFN-γ). Intrapulmonary IFN-γ increases pulmonary IFN-γ-producing T lymphocytes through the CXCR3 pathway. Virus-infected mice lacking IP-10/CXCR3 demonstrate lower pulmonary neutrophilic inflammation. AMG487, an IP-10/CXCR3 antagonist, ameliorates virus-induced lung injury in vivo through decreasing viral loads. This study examined whether AMG487 could treat H1N1 virus-induced mouse illness through reducing viral loads or decreasing the number of lymphocytes or neutrophils | ||
| 520 | |a EXPERIMENTAL APPROACH: Here, we studied the above-mentioned effects and underlying mechanisms in vivo | ||
| 520 | |a KEY RESULTS: H1N1 virus infection caused bad overall condition and pulmonary inflammation characterized by the infiltration of lymphocytes and neutrophils. From Day-5 to Day-10 post-virus infection, bad overall condition, pulmonary lymphocytes, and IFN-γ concentrations increased, while pulmonary H1N1 viral titres and neutrophils decreased. Both anti-IFN-γ and AMG487 alleviated virus infection-induced bad overall condition and pulmonary lymphocytic inflammation. Pulmonary neutrophilic inflammation was mitigated by AMG487 on Day-5 post-infection, but was not mitigated by AMG487 on Day-10 post-infection. H1N1 virus induced increases of IFN-γ, IP-10, and IFN-γ-producing lymphocytes and activation of the Jak2-Stat1 pathways in mouse lungs, which were inhibited by AMG487. Anti-IFN-γ decreased IFN-γ and IFN-γ-producing lymphocytes on Day-5 post-infection. AMG487 but not anti-IFN-γ decreased viral titres in mouse lung homogenates or BALF. Higher virus load did not increase pulmonary inflammation and IFN-γ concentrations when mice were treated with AMG487 | ||
| 520 | |a CONCLUSION AND IMPLICATIONS: AMG487 may ameliorate H1N1 virus-induced pulmonary inflammation through decreasing IFN-γ-producing lymphocytes rather than reducing viral loads or neutrophils | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AMG487 | |
| 650 | 4 | |a CXC chemokine receptor 3 | |
| 650 | 4 | |a influenza a virus | |
| 650 | 4 | |a interferon-γ | |
| 650 | 4 | |a interferon-γ-inducible protein 10 | |
| 700 | 1 | |a Li, Runfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Tongtong |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Zifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Dongting |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Chuqin |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Shuirong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Nanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Kefang |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Zheng |e verfasserin |4 aut | |
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