{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T03:11:03Z","timestamp":1778037063260,"version":"3.51.4"},"update-to":[{"DOI":"10.1038\/nm1103-1433b","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000}}],"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2003,10,1]]},"DOI":"10.1038\/nm939","type":"journal-article","created":{"date-parts":[[2003,9,30]],"date-time":"2003-09-30T20:47:08Z","timestamp":1064954828000},"page":"1245-1250","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":472,"title":["TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases"],"prefix":"10.1038","volume":"9","author":[{"given":"Marc","family":"Feldmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravinder N","family":"Maini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"BFnm939_CR1","doi-asserted-by":"publisher","first-page":"3632","DOI":"10.1073\/pnas.79.11.3632","volume":"72","author":"L Klareskog","year":"1982","unstructured":"Klareskog, L., Forsum, U., Scheynius, A., Kabelitz, D. & Wigzell, H. Evidence in support of a self perpetuating HLA-DR dependent delayed type cell reaction in rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 72, 3632\u20133636 (1982).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm939_CR2","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(81)91107-7","volume":"2","author":"G Janossy","year":"1981","unstructured":"Janossy, G. et al. Rheumatoid arthritis: a disease of T-lymphocyte\/macrophage immunoregulation. Lancet 2, 839\u2013842 (1981).","journal-title":"Lancet"},{"key":"BFnm939_CR3","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/S0140-6736(83)90629-3","volume":"2","author":"GF Bottazzo","year":"1983","unstructured":"Bottazzo, G.F., Pujol-Borrell, R., Hanafusa, T. & Feldmann, M. Role of aberrant HLA-DR expression and antigen presentation in the induction of endocrine autoimmunity. Lancet 2, 1115\u20131119 (1983).","journal-title":"Lancet"},{"key":"BFnm939_CR4","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/302305a0","volume":"302","author":"T Taniguchi","year":"1983","unstructured":"Taniguchi, T. et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature 302, 305\u2013310 (1983).","journal-title":"Nature"},{"key":"BFnm939_CR5","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/312724a0","volume":"312","author":"D Pennica","year":"1984","unstructured":"Pennica, D. et al. Human tumor necrosis factor: precursor structure expression and homology to lymphotoxin. Nature 312, 724\u2013729 (1984).","journal-title":"Nature"},{"key":"BFnm939_CR6","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.1002\/j.1460-2075.1987.tb02598.x","volume":"6","author":"L Yasukawa","year":"1987","unstructured":"Yasukawa, L. et al. Structure and expression of human B cell stimulatory factor-2 (BSF-2\/IL-6 gene). EMBO J. 6, 2939\u20132945 (1987).","journal-title":"EMBO J."},{"key":"BFnm939_CR7","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1146\/annurev.immunol.14.1.397","volume":"14","author":"M Feldmann","year":"1996","unstructured":"Feldmann, M., Brennan, F.M. & Maini, R.N. Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14, 397\u2013440 (1996).","journal-title":"Annu. Rev. Immunol."},{"key":"BFnm939_CR8","first-page":"449","volume":"73","author":"G Buchan","year":"1988","unstructured":"Buchan, G. et al. Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 alpha. Clin. Exp. Immunol. 73, 449\u2013455 (1988).","journal-title":"Clin. Exp. Immunol."},{"key":"BFnm939_CR9","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/S0140-6736(89)90430-3","volume":"2","author":"FM Brennan","year":"1989","unstructured":"Brennan, F.M., Chantry, D., Jackson, A., Maini, R. & Feldmann, M. Inhibitory effect of TNF alpha antibodies on synovial cell interleukin- 1 production in rheumatoid arthritis. Lancet 2, 244\u2013247 (1989).","journal-title":"Lancet"},{"key":"BFnm939_CR10","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1002\/eji.1830211039","volume":"21","author":"C Haworth","year":"1991","unstructured":"Haworth, C. et al. Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur. J. Immunol. 21, 2575\u20132579 (1991).","journal-title":"Eur. J. Immunol."},{"key":"BFnm939_CR11","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1084\/jem.170.5.1627","volume":"170","author":"Y Fong","year":"1989","unstructured":"Fong, Y. et al. Antibodies to cachectin\/tumor necrosis factor reduce interleukin 1\u03b2 and interleukin 6 appearance during lethal bacteremia. J. Exp. Med. 170, 1627\u20131633 (1989).","journal-title":"J. Exp. Med."},{"key":"BFnm939_CR12","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/art.1780340908","volume":"34","author":"CQ Chu","year":"1991","unstructured":"Chu, C.Q., Field, M., Feldmann, M. & Maini, R.N. Localization of tumor necrosis factor \u03b1 in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis Rheum. 34, 1125\u20131132 (1991).","journal-title":"Arthritis Rheum."},{"key":"BFnm939_CR13","doi-asserted-by":"publisher","first-page":"9784","DOI":"10.1073\/pnas.89.20.9784","volume":"89","author":"RO Williams","year":"1992","unstructured":"Williams, R.O., Feldmann, M. & Maini, R.N. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc. Natl. Acad. Sci. USA 89, 9784\u20139788 (1992).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm939_CR14","doi-asserted-by":"publisher","first-page":"4025","DOI":"10.1002\/j.1460-2075.1991.tb04978.x","volume":"10","author":"J Keffer","year":"1991","unstructured":"Keffer, J. et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J. 10, 4025\u20134031 (1991).","journal-title":"EMBO J."},{"key":"BFnm939_CR15","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/330662a0","volume":"330","author":"KJ Tracey","year":"1987","unstructured":"Tracey, K.J. et al. Anti-cachectin\/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330, 662\u2013664 (1987).","journal-title":"Nature"},{"key":"BFnm939_CR16","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1002\/art.1780361206","volume":"36","author":"MJ Elliott","year":"1993","unstructured":"Elliott, M.J. et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum. 36, 1681\u20131690 (1993).","journal-title":"Arthritis Rheum."},{"key":"BFnm939_CR17","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/S0140-6736(94)90632-7","volume":"344","author":"MJ Elliott","year":"1994","unstructured":"Elliott, M.J. et al. Repeated therapy with monoclonal antibody to tumour necrosis factor alpha (cA2) in patients with rheumatoid arthritis. Lancet 344, 1125\u20131127 (1994).","journal-title":"Lancet"},{"key":"BFnm939_CR18","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1016\/S0140-6736(94)90628-9","volume":"344","author":"MJ Elliott","year":"1994","unstructured":"Elliott, M.J. et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344, 1105\u20131110 (1994).","journal-title":"Lancet"},{"key":"BFnm939_CR19","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1002\/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W","volume":"41","author":"RN Maini","year":"1998","unstructured":"Maini, R.N. et al. Randomized placebo-controlled trial of multiple intravenous infusions of anti-TNF\u03b1 monoclonal antibody with or without weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 41, 1552\u20131563 (1998).","journal-title":"Arthritis Rheum."},{"key":"BFnm939_CR20","doi-asserted-by":"publisher","first-page":"2762","DOI":"10.1073\/pnas.91.7.2762","volume":"91","author":"RO Williams","year":"1994","unstructured":"Williams, R.O., Mason, L.J., Feldmann, M. & Maini, R.N. Synergy between anti-CD4 and anti-tumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc. Natl. Acad. Sci. USA 91, 2762\u20132766 (1994).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFnm939_CR21","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1056\/NEJM199707173370301","volume":"337","author":"LW Moreland","year":"1997","unstructured":"Moreland, L.W. et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N. Engl. J. Med. 337, 141\u2013147 (1997).","journal-title":"N. Engl. J. Med."},{"key":"BFnm939_CR22","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1002\/art.10697","volume":"48","author":"ME Weinblatt","year":"2003","unstructured":"Weinblatt, M.E. et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibodiy, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 48, 35\u201345 (2003).","journal-title":"Arthritis Rheum."},{"key":"BFnm939_CR23","doi-asserted-by":"crossref","unstructured":"ATTRACT Study Group. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N. Engl. J. Med. 343, 1594\u20131602 (2000).","DOI":"10.1056\/NEJM200011303432202"},{"key":"BFnm939_CR24","unstructured":"ATTRACT Study Group. Sustained improvement in physical function, structural damage, and signs and symptom through 2 years in rheumatoid arthritis patients treated with infliximab (Remicade) and methotrexate. Arthritis Rheum. (in the press)."},{"key":"BFnm939_CR25","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.4049\/jimmunol.163.3.1521","volume":"163","author":"P Charles","year":"1999","unstructured":"Charles, P. et al. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis. J. Immunol. 163, 1521\u20131528 (1999).","journal-title":"J. Immunol."},{"key":"BFnm939_CR26","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/1529-0131(200001)43:1<38::AID-ANR6>3.0.CO;2-L","volume":"43","author":"PC Taylor","year":"2000","unstructured":"Taylor, P.C. et al. Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor \u03b1 blockade in patients with rheumatoid arthritis. Arthritis Rheum. 43, 38\u201347 (2000).","journal-title":"Arthritis Rheum."},{"key":"BFnm939_CR27","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1002\/1529-0131(199807)41:7<1258::AID-ART17>3.0.CO;2-1","volume":"41","author":"EM Paleolog","year":"1998","unstructured":"Paleolog, E.M. et al. Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis. Arthritis Rheum. 41, 1258\u20131265 (1998).","journal-title":"Arthritis Rheum."},{"key":"BFnm939_CR28","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/S0140-6736(02)07718-8","volume":"359","author":"R Day","year":"2002","unstructured":"Day, R. Adverse reactions to TNF\u03b1 inhibitors in rheumatoid arthritis. Lancet 359, 540\u2013541 (2002).","journal-title":"Lancet"},{"key":"BFnm939_CR29","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1002\/art.1780380202","volume":"38","author":"WP Arend","year":"1995","unstructured":"Arend, W.P. & Dayer, J.-M. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor \u03b1 in rheumatoid arthritis. Arthritis Rheum. 38, 151\u2013160 (1995).","journal-title":"Arthritis Rheum."},{"key":"BFnm939_CR30","first-page":"1426","volume":"30","author":"N Nishimoto","year":"2003","unstructured":"Nishimoto, N. et al. Toxicity, pharmacokinetics, and dose-finding study of repetitive treatment with the humanized anti-interleukin receptor antibody MRA in rheumatoid arthritis. Phase I\/II clinical study. J. Rheumatol. 30, 1426\u20131435 (2003).","journal-title":"J. Rheumatol."},{"key":"BFnm939_CR31","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1146\/annurev.immunol.19.1.163","volume":"19","author":"M Feldmann","year":"2001","unstructured":"Feldmann, M. & Maini, R.N. Anti-TNF\u03b1 therapy or rheumatoid arthritis: What have we learned? Annu. Rev. Immunol. 19, 163\u2013196 (2001).","journal-title":"Annu. Rev. Immunol."},{"key":"BFnm939_CR32","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/0016-5085(95)90277-5","volume":"109","author":"HM van Dullemen","year":"1995","unstructured":"van Dullemen, H.M. et al. Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 109, 129\u2013135 (1995).","journal-title":"Gastroenterology"}],"updated-by":[{"DOI":"10.1038\/nm1103-1433b","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2003,11,1]],"date-time":"2003-11-01T00:00:00Z","timestamp":1067644800000}}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nm939.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm939","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nm939.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T22:35:21Z","timestamp":1684449321000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nm939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,1]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2003,10,1]]}},"alternative-id":["BFnm939"],"URL":"https:\/\/doi.org\/10.1038\/nm939","relation":{"erratum":[{"id-type":"doi","id":"10.1038\/nm1103-1433b","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10,1]]}}}