{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:14:36Z","timestamp":1791188076072,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0107886","type":"journal-article","created":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T17:51:20Z","timestamp":1412185880000},"page":"e107886","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":72,"title":["IL-6 Amplifies TLR Mediated Cytokine and Chemokine Production: Implications for the Pathogenesis of Rheumatic Inflammatory Diseases"],"prefix":"10.1371","volume":"9","author":[{"given":"Ivan","family":"Caiello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetana","family":"Minnone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Holzinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Vogl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusi","family":"Prencipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Manzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"De Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Strippoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/ncprheum0338","article-title":"Interleukin 6: from bench to bedside","volume":"2","author":"N Nishimoto","year":"2006","journal-title":"Nat Clin Pract Rheumatol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20030407","article-title":"Principles of interleukin (IL)-6-type cytokine signalling and its regulation","volume":"374","author":"PC Heinrich","year":"2003","journal-title":"Biochem J"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.molmed.2007.12.007","article-title":"The wolf in sheep\u2019s clothing: the role of interleukin-6 in immunity, inflammation and cancer","volume":"14","author":"WE Naugler","year":"2008","journal-title":"Trends Mol Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1056\/NEJMoa1112802","article-title":"Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis","volume":"367","author":"F De Benedetti","year":"2012","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S0140-6736(08)60453-5","article-title":"Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial","volume":"371","author":"JS Smolen","year":"2008","journal-title":"Lancet"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis","volume":"51","author":"E Choy","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.immuni.2008.07.018","article-title":"Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction","volume":"29","author":"H Ogura","year":"2008","journal-title":"Immunity"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1002\/art.34477","article-title":"Brief report: inhibition of interleukin-6 function corrects Th17\/Treg cell imbalance in patients with rheumatoid arthritis","volume":"64","author":"M Samson","year":"2012","journal-title":"Arthritis Rheum"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"O Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1189\/jlb.1209775","article-title":"Endogenous ligands of TLR2 and TLR4: agonists or assistants?","volume":"87","author":"C Erridge","year":"2010","journal-title":"J Leukoc Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1136\/annrheumdis-2012-201329","article-title":"Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study","volume":"71","author":"J Gerss","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1136\/annrheumdis-2011-200598","article-title":"The Toll-like receptor 4 agonist MRP8\/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis","volume":"71","author":"D Holzinger","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/art.30081","article-title":"Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcgamma receptor","volume":"63","author":"J Sokolove","year":"2011","journal-title":"Arthritis Rheum"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/art.33496","article-title":"Amplification of the response to Toll-like receptor ligands by prolonged exposure to interleukin-6 in mice: implication for the pathogenesis of macrophage activation syndrome","volume":"64","author":"R Strippoli","year":"2012","journal-title":"Arthritis Rheum"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"R101","DOI":"10.1186\/ar2302","article-title":"Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure","volume":"9","author":"CA Scire","year":"2007","journal-title":"Arthritis Res Ther"},{"key":"ref16","first-page":"1403","article-title":"Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis","volume":"24","author":"F De Benedetti","year":"1997","journal-title":"J Rheumatol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1182\/blood.V75.1.40.40","article-title":"Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF","volume":"75","author":"R Schindler","year":"1990","journal-title":"Blood"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/ar2457","article-title":"The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis","volume":"10","author":"KD Brown","year":"2008","journal-title":"Arthritis Res Ther"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"55633","DOI":"10.1074\/jbc.M409825200","article-title":"Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription","volume":"279","author":"H Buss","year":"2004","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1242\/jcs.071647","article-title":"p38 maintains E-cadherin expression by modulating TAK1-NF-kappa B during epithelial-to-mesenchymal transition","volume":"123","author":"R Strippoli","year":"2010","journal-title":"J Cell Sci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.4049\/jimmunol.1300825","article-title":"Nerve Growth Factor Downregulates Inflammatory Response in Human Monocytes through TrkA","volume":"192","author":"G Prencipe","year":"2014","journal-title":"J Immunol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/intimm\/12.2.187","article-title":"IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor","volume":"12","author":"N Nishimoto","year":"2000","journal-title":"Int Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1172\/JCI1368","article-title":"IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses","volume":"101","author":"Z Xing","year":"1998","journal-title":"J Clin Invest"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.bbamcr.2011.01.034","article-title":"The pro- and anti-inflammatory properties of the cytokine interleukin-6","volume":"1813","author":"J Scheller","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1084\/jem.187.4.461","article-title":"Interleukin 6 is required for the development of collagen-induced arthritis","volume":"187","author":"T Alonzi","year":"1998","journal-title":"J Exp Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1084\/jem.180.4.1243","article-title":"Defective inflammatory response in interleukin 6-deficient mice","volume":"180","author":"E Fattori","year":"1994","journal-title":"J Exp Med"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.4049\/jimmunol.143.11.3517","article-title":"IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice","volume":"143","author":"D Aderka","year":"1989","journal-title":"J Immunol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1056\/NEJMoa1205099","article-title":"Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis","volume":"367","author":"N Ruperto","year":"2012","journal-title":"N Engl J Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/eji.201040319","article-title":"IL-1: discoveries, controversies and future directions","volume":"40","author":"CA Dinarello","year":"2010","journal-title":"Eur J Immunol"},{"key":"ref30","unstructured":"Stein N, Witt M, Baeuerle M, Proft F, Schulze-Koops H, <etal>et al<\/etal>.. (2012) Familial Mediterranean Fever: Inhibition of IL-6 Signalling As a New Therapeutic Option in a Frequent Autoinflammatory Syndrome. ACR abstract 747."},{"key":"ref31","doi-asserted-by":"crossref","first-page":"3194","DOI":"10.4049\/jimmunol.171.6.3194","article-title":"IL-6 induces NF-kappa B activation in the intestinal epithelia","volume":"171","author":"L Wang","year":"2003","journal-title":"J Immunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1074\/jbc.M311498200","article-title":"Interleukin 1 activates STAT3\/nuclear factor-kappaB cross-talk via a unique TRAF6- and p65-dependent mechanism","volume":"279","author":"Y Yoshida","year":"2004","journal-title":"J Biol Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1128\/IAI.72.7.3823-3828.2004","article-title":"In vivo interleukin-6 protects neutrophils from apoptosis in osteomyelitis","volume":"72","author":"V Asensi","year":"2004","journal-title":"Infect Immun"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/82763","article-title":"IL-6 switches the differentiation of monocytes from dendritic cells to macrophages","volume":"1","author":"P Chomarat","year":"2000","journal-title":"Nat Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.immuni.2012.05.008","article-title":"The chemokine superfamily revisited","volume":"36","author":"A Zlotnik","year":"2012","journal-title":"Immunity"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1002\/art.21273","article-title":"RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3","volume":"52","author":"F Brentano","year":"2005","journal-title":"Arthritis Rheum"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0107886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,16]],"date-time":"2023-07-16T23:44:07Z","timestamp":1689551047000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0107886"}},"subtitle":[],"editor":[{"given":"Wenyu","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0107886","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,1]]}}}