{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:49:57Z","timestamp":1791384597236,"version":"4.3.3"},"reference-count":77,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T00:00:00Z","timestamp":1668297600000},"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":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Leflunomide is a classic disease\u2010modifying anti\u2010rheumatic drug that is widely used to treat autoimmune diseases. Studies also show its antiviral effects in <jats:italic>in vitro<\/jats:italic> and\/or <jats:italic>in vivo<\/jats:italic> experiments. Considering glucocorticoids, immunosuppressants and newly emerged antibodies commonly used in autoimmune diseases and autoinflammatory disorders bring risk of infection such as viral infection, leflunomide with combination of anti\u2010viral and immunosuppressive features to maintain the balance between infection and anti\u2010inflammation are attractive. Here we summarize the actions and mechanisms of leflunomide in immunoregulatory and antiviral effects.<\/jats:p>","DOI":"10.1111\/1756-185x.14491","type":"journal-article","created":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T16:59:40Z","timestamp":1668358780000},"page":"195-209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Leflunomide: Traditional immunosuppressant with concurrent antiviral effects"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7266-8016","authenticated-orcid":false,"given":"Kunyu","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-8068","authenticated-orcid":false,"given":"Chengmei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0899-5703","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengtao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences &amp; Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID), Ministry of Science &amp; Technology; State Key Laboratory of Complex Severe and Rare Diseases, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education Peking Union Medical College Hospital (PUMCH)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3062.2011.00682.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2020.102468"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301848w"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.21.2542"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.6.655"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.098467"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)09403-3"},{"key":"e_1_2_9_9_1","first-page":"1228","article-title":"Leflunomide, a new disease\u2010modifying drug for treating active rheumatoid arthritis in methotrexate\u2010controlled phase II clinical trial","volume":"116","author":"Bao C","year":"2003","journal-title":"Chin Med J"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.21.2542"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529\u20100131(200109)44:9<::AID\u2010ART346>3.0.CO;2\u2010B"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4368-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4348-z"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.044248"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144548"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-009-0861-3"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201026"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(20)30057-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.060905"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20253"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000091251"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.21848"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2004.05836.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00124743-200112000-00003"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem029"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh009"},{"key":"e_1_2_9_27_1","first-page":"67","article-title":"Methotrexate plus leflunomide for the treatment of relapsingWegener's granulomatosis. A retrospective uncontrolled study","volume":"28","author":"Bremer JP","year":"2010","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-007-0643-9"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2012.02981.x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2019.06.009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X20947296"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2009.05.004"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.01152.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.105982"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1693497"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2005.06.002"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.4.2095"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1131-x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-222486"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.14319"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000001703"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2022.152018"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000053979"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199909270-00014"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2004.03.007"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3181e94106"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.13176"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.01.016"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.12659\/AOT.884035"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704694"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.13733"},{"key":"e_1_2_9_52_1","first-page":"2201","article-title":"Leflunomide\u2010associated infections in rheumatoid arthritis","volume":"34","author":"Jenks KA","year":"2007","journal-title":"J Rheumatol"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200101150-00031"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2012.02.026"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17863"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr416"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318264351e"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0784"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12110"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200503173521125"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000000407"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1159\/000345852"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01737-09"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182007be2"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.04.037"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01779-10"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111331"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1086\/345905"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109305"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25024"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1763"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-011-9578-7"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00768-w"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12250-020-00258-7"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi4708"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1417"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.581833"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-022-06157-4"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.14491","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1756-185X.14491","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.14491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T18:45:30Z","timestamp":1692557130000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.14491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,13]]},"references-count":77,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/1756-185X.14491"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.14491","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,13]]},"assertion":[{"value":"2022-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}