{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:02:34Z","timestamp":1791356554328,"version":"4.3.1"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,2,4]],"date-time":"2003-02-04T00:00:00Z","timestamp":1044316800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the expression patterns of interkeukin\u201018 (IL\u201018) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin\u2010embedded, snap\u2010frozen sections were used for immunohistochemical detection of IL\u201018, tumor necrosis factor \u03b1 (TNF\u03b1), IL\u20101\u03b2, IL\u201012, and IL\u201017. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E\u2010selectin, and cell markers CD3, CD14, and CD68 were stained.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL\u201018 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL\u201018 expression in the synovial tissue was strongly correlated with the expression of IL\u20101\u03b2 (in the sublining r = 0.72, in the lining r = 0.71; both <jats:italic>P<\/jats:italic> &lt; 0.0001) and TNF\u03b1 (in the sublining r = 0.59, <jats:italic>P<\/jats:italic> &lt; 0.0007, and in the lining r = 0.68, <jats:italic>P<\/jats:italic> &lt; 0.0001). In addition, IL\u201018 expression in the sublining correlated with macrophage infiltration (r = 0.64, <jats:italic>P<\/jats:italic> &lt; 0.0007) and microscopic inflammation scores (r = 0.78, <jats:italic>P<\/jats:italic> &lt; 0.0001), and with the acute\u2010phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, <jats:italic>P<\/jats:italic> &lt; 0.0004). Interestingly, RA synovial tissue that coexpressed IL\u201018 and IL\u201012 demonstrated enhanced levels of the Th1\u2010associated cytokine IL\u201017.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results show that expression of IL\u201018 is associated with that of IL\u20101\u03b2 and TNF\u03b1 and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL\u201018 expression correlates with the acute\u2010phase response. These data indicate that IL\u201018 is a primary proinflammatory cytokine in RA that drives the local production of IL\u20101\u03b2 and TNF\u03b1.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10814","type":"journal-article","created":{"date-parts":[[2003,2,7]],"date-time":"2003-02-07T07:09:02Z","timestamp":1044601742000},"page":"339-347","source":"Crossref","is-referenced-by-count":109,"title":["Association of interleukin\u201018 expression with enhanced levels of both interleukin\u20101\u03b2 and tumor necrosis factor \u03b1 in knee synovial tissue of patients with rheumatoid arthritis"],"prefix":"10.1002","volume":"48","author":[{"given":"Leo A. B.","family":"Joosten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R. D.","family":"Radstake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lubberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liduine A. M.","family":"van den Bersselaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet L. C. M.","family":"van Riel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L. E. M.","family":"van Lent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Barrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim B.","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,2,4]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380202"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.397"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90628-9"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.163"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.4.311"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199812)41:12<2196::AID-ART15>3.0.CO;2-2"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10141"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7317"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200102)44:2<275::AID-ANR44>3.0.CO;2-B"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.57.2.590-595.1989"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/378088a0"},{"key":"e_1_2_5_13_2","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.4049\/jimmunol.156.11.4274","article-title":"Cloning of the cDNA for human IFN\u2010gamma\u2010inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein","volume":"156","author":"Ushio S","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_5_14_2","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.4049\/jimmunol.158.4.1541","article-title":"IFN\u2010gamma\u2010inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL\u201012","volume":"158","author":"Kohno K","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)00051-5"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60389-2"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80543-9"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1379"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.8.723"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.8.726"},{"key":"e_1_2_5_21_2","first-page":"1779","article-title":"Mature form of interleukin 18 is expressed in rheumatoid arthritis synovial tissue and contributes to interferon\u2010gamma production by synovial T cells","volume":"28","author":"Tanaka M","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780351"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103574200"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1644"},{"key":"e_1_2_5_25_2","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.4049\/jimmunol.162.2.1096","article-title":"IL\u201018 is produced by articular chondrocytes and induces proinflammatory and catabolic responses","volume":"162","author":"Olee T","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6553"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.517"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.12.6495"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112097"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.49.11.916"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400807"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.60.7.660"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.423"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3075"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011022"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.12.7014"},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar294"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.1004"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5703"},{"key":"e_1_2_5_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200105)44:5<1003::AID-ANR179>3.0.CO;2-#"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(01)00682-2"},{"key":"e_1_2_5_43_2","first-page":"483","article-title":"Interleukin\u201018, a proinflammatory cytokine","volume":"11","author":"Dinarello CA","year":"2000","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_5_44_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.72.1.192"},{"key":"e_1_2_5_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2879"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.10814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T17:13:54Z","timestamp":1697044434000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.10814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,2]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,2]]}},"alternative-id":["10.1002\/art.10814"],"URL":"https:\/\/doi.org\/10.1002\/art.10814","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,2]]}}}