{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:49:28Z","timestamp":1785865768347,"version":"3.56.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":820,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>The chemokine receptor CCR1 is a potential target for the treatment of rheumatoid arthritis. To explore the impact of CCR1 blockade in experimental arthritis and the underlying mechanisms, we used J\u2010113863, a non\u2010peptide antagonist of the mouse receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Compound J\u2010113863 was tested in collagen\u2010induced arthritis (CIA) and three models of acute inflammation;<jats:italic>Staphylococcus<\/jats:italic>enterotoxin B (SEB)\u2010induced interleukin\u20102 (IL\u20102), delayed\u2010type hypersensitivity (DTH) response, and lipopolysaccharide (LPS)\u2010induced tumour necrosis factor\u03b1 (TNF\u03b1) production. In the LPS model, CCR1 knockout, adrenalectomised, or IL\u201010\u2010depleted mice were also used. Production of TNF\u03b1 by mouse macrophages and human synovial membrane samples in vitro were also studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Treatment of arthritic mice with J\u2010113863 improved paw inflammation and joint damage, and dramatically decreased cell infiltration into joints. The compound did not inhibit IL\u20102 or DTH, but reduced plasma TNF\u03b1 levels in LPS\u2010treated mice. Surprisingly, CCR1 knockout mice produced more TNF\u03b1 than controls in response to LPS, and J\u2010113863 decreased TNF\u03b1 also in CCR1 null mice, indicating that its effect was unrelated to CCR1. Adrenalectomy or neutralisation of IL\u201010 did not prevent inhibition of TNF\u03b1 production by J\u2010113863. The compound did not inhibit mouse TNF\u03b1 in vitro, but did induce a trend towards increased TNF\u03b1 release in cells from synovial membranes of rheumatoid arthritis patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>CCR1 blockade improves the development of CIA, probably via inhibition of inflammatory cell recruitment. However, results from both CCR1\u2010deficient mice and human synovial membranes suggest that, in some experimental settings, blocking CCR1 could enhance TNF production.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2006)<jats:bold>149<\/jats:bold>, 666\u2013675. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706912\">10.1038\/sj.bjp.0706912<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706912","type":"journal-article","created":{"date-parts":[[2006,10,3]],"date-time":"2006-10-03T11:10:04Z","timestamp":1159873804000},"page":"666-675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks<i>in vivo<\/i>"],"prefix":"10.1111","volume":"149","author":[{"given":"M","family":"Amat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C F","family":"Benjamim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Prats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Terricabras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Beleta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S L","family":"Kunkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Godessart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000130082.67775.60"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214040"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.3.1564"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.8.4070"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706243"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0022-3565(24)36487-0","article-title":"The phosphodiesterase type 4 (PDE4) inhibitor CP\u201080,633 elevates plasma cyclic AMP levels and decreases tumor necrosis factor\u2010alpha (TNFalpha) production in mice: effect of adrenalectomy","volume":"280","author":"Cheng J","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2005.03.012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.13.4046"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2003.09.010"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8126"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.11.1959"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6467"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306875200"},{"key":"e_1_2_8_15_1","first-page":"499","article-title":"CCR1 antagonists for the treatment of autoimmune diseases","volume":"5","author":"Gladue R","year":"2004","journal-title":"Current Opinion Invest Drugs"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1361.109"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(01)00277-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.8.715"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-2023(02)00361-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M007457200"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200105)44:5<1022::AID-ANR181>3.0.CO;2-N"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20932"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200102)44:2<442::AID-ANR63>3.0.CO;2-M"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.3392"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001222200"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00863-8"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(02)00045-X"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0031-6997(24)01439-X","article-title":"International union of pharmacology. 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