{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:57:03Z","timestamp":1761058623034},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,12,9]],"date-time":"2005-12-09T00:00:00Z","timestamp":1134086400000},"content-version":"vor","delay-in-days":6096,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1989,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To explore the possibility that the mechanism of action of methotrexate (MTX) in rheumatoid arthritis (RA) is related to modulation of interleukin\u20101 (IL\u20101), the effects of MTX on IL\u20101 production and activity were evaluated. Human peripheral blood mononuclear cells and murine peritoneal and splenic cells were stimulated by lipopolysaccharide to produce IL\u20101. No inhibition of IL\u20101 synthesis or secretion caused by MTX treatment could be demonstrated either in vitro or in vivo, in patients with RA or in mice treated with MTX. We did show, however, that MTX had an inhibitory effect on IL\u20101 activity in 2 assays that demonstrate 2 different functions of IL\u20101. In a 2\u2010step assay using LBRM\u201033\u20101A5 (1A5) and CTLD cells, MTX inhibited the secretion of IL\u20102 by 1A5 lymphoma cells in response to phytohemag\u2010glutinin and IL\u20101. In an assay using D10.G4.1 (D10) cells, MTX inhibited IL\u20101\u2013induced proliferation of the D10 T cell clone. No effect of the drug on IL\u20102 activity was observed. The results demonstrate that MTX is capable of inhibiting some IL\u20101 activities without affecting IL\u20101 production or secretion. We propose that the inhibition of IL\u20101 activity or IL\u20101\u2013dependent events may be one of the mechanisms of action of MTX in RA.<\/jats:p>","DOI":"10.1002\/anr.1780320403","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T23:16:09Z","timestamp":1171494969000},"page":"370-377","source":"Crossref","is-referenced-by-count":99,"title":["The effects of methotrexate on the production and activity of interleukin\u20101"],"prefix":"10.1002","volume":"32","author":[{"given":"Rafael","family":"Segal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edna","family":"Mozes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Yaron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Tartakovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,14]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198503283121303"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-103-4-489"},{"key":"e_1_2_1_4_2","first-page":"294","article-title":"Measurement of immunologic and inflammatory responses in vitro in rheumatoid arthritis patients treated with methotrexate","volume":"13","author":"Johnson CA","year":"1986","journal-title":"J Rheumatol"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780300501"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198503283121310"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/6.1.51"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00541245"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780260806"},{"key":"e_1_2_1_10_2","first-page":"293","article-title":"Enhanced IL\u20101 generation by monocytes in vitro is temporarily linked to an early event in the onset of exacerbation of rheumatoid arthritis","volume":"65","author":"Shore A","year":"1986","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_1_11_2","first-page":"598","article-title":"Enhanced interleukin 1 and depressed interleukin 2 production in juvenile arthritis","volume":"13","author":"Martini A","year":"1986","journal-title":"J Rheumatol"},{"key":"e_1_2_1_12_2","first-page":"33","article-title":"Interleukin\u20101 secretion by peripheral blood monocytes and synovial macrophages from patients with rheumatoid arthritis","volume":"14","author":"Danis VA","year":"1987","journal-title":"J Rheumatol"},{"key":"e_1_2_1_13_2","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.4049\/jimmunol.128.5.2177","article-title":"Interleukin\u20101, a potential regulator of fibroblast proliferation","volume":"128","author":"Schmidt JA","year":"1982","journal-title":"J Immunol"},{"key":"e_1_2_1_14_2","volume-title":"Interactions among lymphocytes, monocytes and other synovial cells in the rheumatoid synovium, Lymphokines","author":"Krane SM","year":"1982"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270113"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.4.2474"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(85)90034-6"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/306378a0"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/XXIV.suppl_1.29"},{"key":"e_1_2_1_20_2","first-page":"1123","article-title":"Effects of gold on the production of and response to human interleukin\u20101","volume":"14","author":"Drakes ML","year":"1987","journal-title":"J Rheumatol"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.2.1133"},{"key":"e_1_2_1_22_2","first-page":"175","article-title":"Induction of receptors for interleukin\u20102 requires T cell Ag: Ia receptor crosslinking and interleukin\u20101","volume":"3","author":"Kaje J","year":"1984","journal-title":"Lymphokine Res"},{"key":"e_1_2_1_23_2","doi-asserted-by":"crossref","first-page":"4280","DOI":"10.4049\/jimmunol.138.12.4280","article-title":"Autocrine growth of T cells independent of interleukin 2: identification of interleukin 4 (IL\u20104, BSF\u20101) as an autocrine growth factor for a cloned antigen\u2010specific helper T cell","volume":"138","author":"Kupper T","year":"1987","journal-title":"J Immunol"},{"key":"e_1_2_1_24_2","first-page":"175","article-title":"1958 revision of diagnostic criteria for rheumatoid arthritis","volume":"9","author":"Ropes MW","year":"1958","journal-title":"Bull Rheum Dis"},{"key":"e_1_2_1_25_2","unstructured":"SegalR CaspiD TishlerM ViglerI YaronM:Short term effects of low dose methotrexate on the acute phase reaction in rheumatoid arthritis patients. Submitted for publication."},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290703"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(84)90024-X"},{"key":"e_1_2_1_28_2","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.4049\/jimmunol.131.3.1280","article-title":"A rapid biologic assay for the detection of interleukin 1","volume":"131","author":"Conlon PJ","year":"1983","journal-title":"J Immunol"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fanr.1780320403","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anr.1780320403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T20:13:42Z","timestamp":1700684022000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anr.1780320403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,4]]},"references-count":27,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1989,4]]}},"alternative-id":["10.1002\/anr.1780320403"],"URL":"https:\/\/doi.org\/10.1002\/anr.1780320403","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[1989,4]]}}}