{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:30:25Z","timestamp":1789237825642,"version":"build-2803163510"},"reference-count":89,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a complex systemic disorder characterized primarily by articular inflammation and destruction with associated functional loss and reduced quality of life. RA is also associated with extra\u2010articular disease, such as that of the lung, with potentially devastating clinical consequences. The critical importance of comorbidities, and consequent multimorbidity, in determining outcomes in RA has now been recognized, not least as novel therapeutics have emerged with attendant increased life expectancy. The primary role of cytokine networks in mediating RA pathogenesis was established in extensive preclinical and clinical trials and in the adoption of cytokine\u2010targeted therapeutics in clinical care over three decades. Herein, we briefly review those pivotal cytokine pathways that are associated with RA articular disease and extend these insights to include extra\u2010articular RA and its common comorbidities.<\/jats:p>","DOI":"10.1002\/art.43376","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T08:02:01Z","timestamp":1757404921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cytokine Pathways Driving Diverse Tissue Pathologies in Rheumatoid Arthritis"],"prefix":"10.1002","author":[{"given":"Aurelie","family":"Najm","sequence":"first","affiliation":[{"name":"School of Infection and Immunity, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6136-8349","authenticated-orcid":false,"given":"Lyn D.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-8501","authenticated-orcid":false,"given":"Iain B.","family":"McInnes","sequence":"additional","affiliation":[{"name":"College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.11.004"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.11.009"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2959"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25265"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00183-2"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/89782"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.120886"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214827"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep329"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222010922"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.007"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11143"},{"issue":"1","key":"e_1_2_3_16_1","doi-asserted-by":"crossref","first-page":"41411","DOI":"10.1038\/srep41411","article-title":"Combination of IL\u20106 and sIL\u20106R differentially regulate varying levels of RANKL\u2010induced osteoclastogenesis through NF\u2010\u03baB, ERK and JNK signaling pathways","volume":"7","author":"Feng W","year":"2017","journal-title":"Sci Rep"},{"key":"e_1_2_3_17_1","first-page":"iii2","article-title":"The role of interleukin\u20101 in the pathogenesis of rheumatoid arthritis","volume":"43","author":"Kay J","year":"2004","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(02)00021-7"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2018.1486819"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60389-2"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00289"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.016428"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10825"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63357-3"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00726-8"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1202117"},{"key":"e_1_2_3_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003668"},{"issue":"4","key":"e_1_2_3_28_1","first-page":"3498","article-title":"JAK\/STAT pathway in pathology of rheumatoid arthritis (Review)","volume":"20","author":"Ciobanu DA","year":"2020","journal-title":"Exp Ther Med"},{"key":"e_1_2_3_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.161"},{"key":"e_1_2_3_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.7.3639"},{"key":"e_1_2_3_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224449"},{"key":"e_1_2_3_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.146225"},{"key":"e_1_2_3_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202450"},{"key":"e_1_2_3_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2094"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.11.5654"},{"key":"e_1_2_3_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5818"},{"key":"e_1_2_3_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078619"},{"key":"e_1_2_3_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21249"},{"key":"e_1_2_3_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200726"},{"key":"e_1_2_3_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-016-3638-5"},{"key":"e_1_2_3_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00596-8"},{"key":"e_1_2_3_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08213-2"},{"key":"e_1_2_3_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2045"},{"key":"e_1_2_3_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206624"},{"key":"e_1_2_3_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809798"},{"key":"e_1_2_3_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002867"},{"issue":"9","key":"e_1_2_3_47_1","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1002\/art.22809","article-title":"British Society for Rheumatology Biologics Register Control Centre Consortium; British Society for Rheumatology Biologics Register. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti\u2010tumor necrosis factor \u03b1 therapy: results from the British Society for Rheumatology Biologics Register","volume":"56","author":"Dixon WG","year":"2007","journal-title":"Arthritis Rheum"},{"key":"e_1_2_3_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223302"},{"key":"e_1_2_3_49_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217653"},{"key":"e_1_2_3_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-00969-7"},{"key":"e_1_2_3_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1882"},{"issue":"1","key":"e_1_2_3_52_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1093\/cvr\/cvad158","article-title":"TNF\u2010\u03b1 protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart\u2010reactive CD4+ T cells","volume":"120","author":"Rolski F","year":"2024","journal-title":"Cardiovasc Res"},{"key":"e_1_2_3_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1752-8062.2008.00013.x"},{"issue":"2","key":"e_1_2_3_54_1","first-page":"319","article-title":"Cardiovascular risk assessment in rheumatoid arthritis: accelerated atherosclerosis, new biomarkers, and the effects of biological therapy","volume":"13","author":"Popescu D","year":"2023","journal-title":"Life (Basel)"},{"key":"e_1_2_3_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211708"},{"key":"e_1_2_3_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204345"},{"key":"e_1_2_3_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-021-00304-0"},{"key":"e_1_2_3_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41095"},{"key":"e_1_2_3_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht367"},{"key":"e_1_2_3_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60484-9"},{"key":"e_1_2_3_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00520-1"},{"key":"e_1_2_3_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-273417"},{"issue":"12","key":"e_1_2_3_63_1","doi-asserted-by":"crossref","first-page":"I308","DOI":"10.1161\/hc37t1.094871","article-title":"Overexpression of interleukin\u20101 receptor antagonist provides cardioprotection against ischemia\u2010reperfusion injury associated with reduction in apoptosis","volume":"104","author":"Suzuki K","year":"2001","journal-title":"Circulation"},{"key":"e_1_2_3_64_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_3_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.02.008"},{"key":"e_1_2_3_66_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109927"},{"key":"e_1_2_3_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052449"},{"key":"e_1_2_3_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2008.06.014"},{"key":"e_1_2_3_69_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0011-2021"},{"key":"e_1_2_3_70_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/759760"},{"issue":"6","key":"e_1_2_3_71_1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1136\/ard.2009.120626","article-title":"BSRBR Control Centre Consortium; British Society for Rheumatology Biologics Register. Influence of anti\u2010TNF therapy on mortality in patients with rheumatoid arthritis\u2010associated interstitial lung disease: results from the British Society for Rheumatology Biologics Register","volume":"69","author":"Dixon WG","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_3_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2010.11.002"},{"key":"e_1_2_3_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.04.021"},{"key":"e_1_2_3_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/imj.14670"},{"issue":"64","key":"e_1_2_3_75_1","first-page":"747","article-title":"Effect of tocilizumab on interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA)","volume":"56","author":"Otsuji N","year":"2020","journal-title":"Eur Respir J"},{"key":"e_1_2_3_76_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-018-0728-9"},{"issue":"1","key":"e_1_2_3_77_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s42358-023-00325-z","article-title":"Baricitinib improves pulmonary fibrosis in mice with rheumatoid arthritis\u2010associated interstitial lung disease by inhibiting the Jak2\/Stat3 signaling pathway","volume":"63","author":"Liu H","year":"2023","journal-title":"Adv Rheumatol"},{"key":"e_1_2_3_78_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-1963-2"},{"issue":"8","key":"e_1_2_3_79_1","doi-asserted-by":"crossref","first-page":"e482","DOI":"10.1097\/RHU.0000000000001552","article-title":"Incidence rates of interstitial lung disease events in tofacitinib\u2010treated rheumatoid arthritis patients: post hoc analysis from 21 clinical trials","volume":"27","author":"Citera G","year":"2021","journal-title":"J Clin Rheumatol"},{"key":"e_1_2_3_80_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.3640"},{"key":"e_1_2_3_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88734-2"},{"key":"e_1_2_3_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01037-w"},{"key":"e_1_2_3_83_1","doi-asserted-by":"publisher","DOI":"10.1001\/2013.jamapsychiatry.4"},{"key":"e_1_2_3_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2016.03.003"},{"issue":"7","key":"e_1_2_3_85_1","first-page":"664","article-title":"Evidence for IL\u20101 receptor blockade as a therapeutic strategy for the treatment of depression","volume":"10","author":"Koo JW","year":"2009","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_3_86_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.pnpbp.2017.04.026","article-title":"Effect of antidepressant treatment on peripheral inflammation markers \u2010 a meta\u2010analysis","volume":"80","author":"Wi\u0119d\u0142ocha M","year":"2018","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"e_1_2_3_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2009.03.020"},{"key":"e_1_2_3_88_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-016-1506-9"},{"key":"e_1_2_3_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04648-0"},{"key":"e_1_2_3_90_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.107912"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.43376","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.43376","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.43376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T04:47:07Z","timestamp":1770698827000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.43376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":89,"alternative-id":["10.1002\/art.43376"],"URL":"https:\/\/doi.org\/10.1002\/art.43376","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"assertion":[{"value":"2025-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"art.43376"}}