{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T18:16:56Z","timestamp":1779387416993,"version":"3.53.1"},"reference-count":44,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970013"],"award-info":[{"award-number":["81970013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170034"],"award-info":[{"award-number":["82170034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Severe influenza virus\u2010infected patients have high systemic levels of Th1 cytokines (including IFN\u2010\u03b3). Intrapulmonary IFN\u2010\u03b3 increases pulmonary IFN\u2010\u03b3\u2010producing T lymphocytes through the CXCR3 pathway. Virus\u2010infected mice lacking IP\u201010\/CXCR3 demonstrate lower pulmonary neutrophilic inflammation. AMG487, an IP\u201010\/CXCR3 antagonist, ameliorates virus\u2010induced lung injury in vivo through decreasing viral loads. This study examined whether AMG487 could treat H1N1 virus\u2010induced mouse illness through reducing viral loads or decreasing the number of lymphocytes or neutrophils.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Here, we studied the above\u2010mentioned effects and underlying mechanisms in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>H1N1 virus infection caused bad overall condition and pulmonary inflammation characterized by the infiltration of lymphocytes and neutrophils. From Day\u20105 to Day\u201010 post\u2010virus infection, bad overall condition, pulmonary lymphocytes, and IFN\u2010\u03b3 concentrations increased, while pulmonary H1N1 viral titres and neutrophils decreased. Both anti\u2010IFN\u2010\u03b3 and AMG487 alleviated virus infection\u2010induced bad overall condition and pulmonary lymphocytic inflammation. Pulmonary neutrophilic inflammation was mitigated by AMG487 on Day\u20105 post\u2010infection, but was not mitigated by AMG487 on Day\u201010 post\u2010infection. H1N1 virus induced increases of IFN\u2010\u03b3, IP\u201010, and IFN\u2010\u03b3\u2010producing lymphocytes and activation of the Jak2\u2010Stat1 pathways in mouse lungs, which were inhibited by AMG487. Anti\u2010IFN\u2010\u03b3 decreased IFN\u2010\u03b3 and IFN\u2010\u03b3\u2010producing lymphocytes on Day\u20105 post\u2010infection. AMG487 but not anti\u2010IFN\u2010\u03b3 decreased viral titres in mouse lung homogenates or BALF. Higher virus load did not increase pulmonary inflammation and IFN\u2010\u03b3 concentrations when mice were treated with AMG487.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>AMG487 may ameliorate H1N1 virus\u2010induced pulmonary inflammation through decreasing IFN\u2010\u03b3\u2010producing lymphocytes rather than reducing viral loads or neutrophils.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16343","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T07:32:48Z","timestamp":1710833568000},"page":"2053-2069","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["AMG487 alleviates influenza A (H1N1) virus\u2010induced pulmonary inflammation through decreasing IFN\u2010\u03b3\u2010producing lymphocytes and IFN\u2010\u03b3 concentrations"],"prefix":"10.1111","volume":"181","author":[{"given":"Wenbin","family":"Ding","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runfeng","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifeng","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongting","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuqin","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuirong","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanshan","family":"Zhong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefang","family":"Lai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2203-6384","authenticated-orcid":false,"given":"Zheng","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109395"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc8208"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.41"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00691-08"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4144"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2022.14.6.653"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110675"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.7.3195"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80573-7"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23191"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00186214"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24395"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201203-0508OC"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.09.001"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1086\/520981"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2019.07.009"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2022.105314"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.12.010"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.1.266"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.11.049"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.06.003"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00360.2014"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.99022"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110456"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.7754\/clin.lab.2012.120417"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2018.0073"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00245"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinimag.2021.04.035"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01211-16"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-016-0996-0"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1086\/650581"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00982-5"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.25"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30545-5"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101921-040450"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.08.022"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-157016"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T03:57:19Z","timestamp":1718683039000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":44,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/bph.16343"],"URL":"https:\/\/doi.org\/10.1111\/bph.16343","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,18]]},"assertion":[{"value":"2023-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}