{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:23:52Z","timestamp":1787786632260,"version":"build-2784847793"},"reference-count":110,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Reviews in Medical Virology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The coronavirus disease 2019 (COVID\u201019) has various presentations, of which immune dysregulation or the so\u2010called cytokine storm syndrome (COVID\u2010CSS) is prominent. Even though cytokines are vital regulators of body immunoinflammatory responses, their exaggerated release can be harmful. This hyperinflammatory response is more commonly observed during severe COVID\u201019 infections, caused by the excessive release of pro\u2010inflammatory cytokines, such as interleukin\u20101 (IL\u20101), IL\u20106, IL\u20108, tumour necrosis factor, granulocyte\u2010macrophage colony\u2010stimulating factor, and interferon\u2010gamma, making their blockers and antagonists of great interest as therapeutic options in this condition. Thus, the pathophysiology of excessive cytokine secretion is outlined, and their most important blockers and antagonists are discussed, mainly focussing on tocilizumab, an interleukin\u20106 receptor blocker approved to treat severe COVID\u201019 infections.<\/jats:p>","DOI":"10.1002\/rmv.2372","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T11:17:19Z","timestamp":1653650239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The role of cytokines and their antagonists in the treatment of COVID\u201019 patients"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1085-374X","authenticated-orcid":false,"given":"Zeinab","family":"Mohseni Afshar","sequence":"first","affiliation":[{"name":"Clinical Research Development Center Imam Reza Hospital Kermanshah University of Medical Sciences  Kermanshah Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8733-9370","authenticated-orcid":false,"given":"Mohammad","family":"Barary","sequence":"additional","affiliation":[{"name":"Student Research Committee Virtual School of Medical Education and Management Shahid Beheshti University of Medical Sciences  Tehran Iran"},{"name":"Students' Scientific Research Center (SSRC) Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-7203","authenticated-orcid":false,"given":"Arefeh","family":"Babazadeh","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Tropical Medicine Research Center Health Research Institute Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-7034","authenticated-orcid":false,"given":"Ali","family":"Tavakoli Pirzaman","sequence":"additional","affiliation":[{"name":"Student Research Committee Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-3854","authenticated-orcid":false,"given":"Rezvan","family":"Hosseinzadeh","sequence":"additional","affiliation":[{"name":"Student Research Committee Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0734-1356","authenticated-orcid":false,"given":"Amirmasoud","family":"Alijanpour","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7842-9398","authenticated-orcid":false,"given":"Amirreza","family":"Allahgholipour","sequence":"additional","affiliation":[{"name":"Student Research Committee School of Nursing and Midwifery Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1403-977X","authenticated-orcid":false,"given":"Seyed Rouhollah","family":"Miri","sequence":"additional","affiliation":[{"name":"Cancer Research Center Cancer Institute of Iran Tehran University of Medical Science  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4210-5479","authenticated-orcid":false,"given":"Terence T.","family":"Sio","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Mayo Clinic  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-6818","authenticated-orcid":false,"given":"Mark J. M.","family":"Sullman","sequence":"additional","affiliation":[{"name":"Department of Social Sciences University of Nicosia  Nicosia Cyprus"},{"name":"Department of Life and Health Sciences University of Nicosia  Nicosia Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9966-9289","authenticated-orcid":false,"given":"Kristin","family":"Carson\u2010Chahhoud","sequence":"additional","affiliation":[{"name":"Australian Centre for Precision Health University of South Australia  Adelaide Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-0448","authenticated-orcid":false,"given":"Soheil","family":"Ebrahimpour","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Tropical Medicine Research Center Health Research Institute Babol University of Medical Sciences  Babol Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(20)30079\u20105"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.4149\/bll_2021_003"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.2478\/rjim\u20102020\u20100013"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26232"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/mop.0000000000000974"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medmal.2020.04.002"},{"issue":"2","key":"e_1_2_16_8_1","first-page":"327","article-title":"Induction of pro\u2010inflammatory cytokines (IL\u20101 and IL\u20106) and lung inflammation by Coronavirus\u201019 (COVI\u201019 or SARS\u2010CoV\u20102): anti\u2010inflammatory strategies","volume":"34","author":"Conti P","year":"2020","journal-title":"J Biol Regul Homeost Agents"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16961"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03006\u20102020"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2020.06.012"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.105954"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(20)30404\u20105"},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010020\u201002878\u20107"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2011.0062"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(20)30183\u20105"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.05.008"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01446"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.010"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra2026131"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742\u20102094\u20105\u201045"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.157.3792.1060"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/312721a0"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2007.04.002"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200160"},{"issue":"4","key":"e_1_2_16_26_1","first-page":"225","article-title":"Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF\u2010alpha antibody with the interleukin\u20101 receptor antagonist","volume":"6","author":"Butler DM","year":"1995","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742\u20102094\u20107\u201016"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2009.04.016"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2006.12.008"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102249.2007.03484.x"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020\u20100471\u2010sa"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5557582"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012421"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01093"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa449"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(20)30600\u20107"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103026"},{"key":"e_1_2_16_38_1","doi-asserted-by":"crossref","unstructured":"LiuT ZhangJ YangY et\u00a0al.The potential role of IL\u20106 in monitoring coronavirus disease 2019. Available at SSRN 3548761.2020.","DOI":"10.2139\/ssrn.3548761"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102572"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1631"},{"key":"e_1_2_16_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00447"},{"key":"e_1_2_16_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2021.105295"},{"key":"e_1_2_16_43_1","article-title":"Interleukin\u20108 as a biomarker for disease prognosis of coronavirus disease\u20102019 patients","volume":"11","author":"Li L","year":"2020","journal-title":"Front Immunol"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155438"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.10.012"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139834"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194\u2010021\u201001268\u2010w"},{"key":"e_1_2_16_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.602130"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.05.072"},{"key":"e_1_2_16_50_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.9658"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26165"},{"key":"e_1_2_16_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-31696-5.00062-0"},{"key":"e_1_2_16_53_1","doi-asserted-by":"publisher","DOI":"10.5937\/afmnai38\u201026326"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.03.062"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.17023"},{"key":"e_1_2_16_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11135"},{"key":"e_1_2_16_57_1","volume-title":"Reducing mortality from septic shock using an interleukin\u20101 receptor antagonist","author":"Chung J","year":"2017"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2018.1486819"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2016.1217988"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.2147\/opth.s68595"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102013\u2010204963"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.06.009"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41927\u2010017\u20100004\u20105"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2665\u20109913(21)00012\u20106"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11030258"},{"key":"e_1_2_16_66_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.6615"},{"key":"e_1_2_16_67_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2028836"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2020.10.020"},{"key":"e_1_2_16_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00676\u20100"},{"key":"e_1_2_16_70_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejme2103108"},{"key":"e_1_2_16_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121\u2010020\u201000326\u20101"},{"key":"e_1_2_16_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102726"},{"key":"e_1_2_16_73_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11947"},{"key":"e_1_2_16_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.08.031"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.31219\/osf.io\/arfhb"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03022"},{"key":"e_1_2_16_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010020\u20100516\u20106"},{"key":"e_1_2_16_78_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.16485"},{"key":"e_1_2_16_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2020.11.005"},{"key":"e_1_2_16_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2013.03.005"},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq242"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2020.08.038"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41285"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102020\u2010218122"},{"key":"e_1_2_16_85_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102020\u2010218243"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(21)00139\u20109"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201074001\u20103"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2020.07.023"},{"key":"e_1_2_16_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102999"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.110053"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.cd013881"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018\u20100028"},{"key":"e_1_2_16_93_1","doi-asserted-by":"publisher","DOI":"10.1097\/mat.0000000000001239"},{"key":"e_1_2_16_94_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2009961117"},{"key":"e_1_2_16_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102564"},{"key":"e_1_2_16_96_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13939"},{"key":"e_1_2_16_97_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102020\u2010000930"},{"key":"e_1_2_16_98_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25907"},{"key":"e_1_2_16_99_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14459"},{"key":"e_1_2_16_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106009"},{"key":"e_1_2_16_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2017.04.002"},{"key":"e_1_2_16_102_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.706482"},{"key":"e_1_2_16_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2020.104659"},{"key":"e_1_2_16_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(16)00232\u20104"},{"key":"e_1_2_16_105_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261\u2010020\u201000917\u20103"},{"key":"e_1_2_16_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.05.030"},{"key":"e_1_2_16_107_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15562"},{"key":"e_1_2_16_108_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14516"},{"key":"e_1_2_16_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2666\u20105247(20)30223\u20108"},{"key":"e_1_2_16_110_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.3313"},{"key":"e_1_2_16_111_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010020\u201006059\u20106"}],"container-title":["Reviews in Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmv.2372","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rmv.2372","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rmv.2372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T16:52:34Z","timestamp":1706892754000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/rmv.2372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,27]]},"references-count":110,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/rmv.2372"],"URL":"https:\/\/doi.org\/10.1002\/rmv.2372","archive":["Portico"],"relation":{},"ISSN":["1052-9276","1099-1654"],"issn-type":[{"value":"1052-9276","type":"print"},{"value":"1099-1654","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,27]]},"assertion":[{"value":"2022-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2372"}}