{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:03:45Z","timestamp":1790737425471,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2002,10,16]],"date-time":"2002-10-16T00:00:00Z","timestamp":1034726400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To test the hypothesis that local activation of melanocortin receptor(s) by adrenocorticotropic hormone (ACTH) could be responsible, at least in part, for its efficacy in human gouty arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Monosodium urate monohydrate (MSU) crystals were administered into rat knee joints either alone or with ACTH or a selective melanocortin type 3 receptor (MC3\u2010R) agonist. Neutrophil migration, arthritis score, increases in joint size, and cytokine levels were measured over time. MC3\u2010R expression on rat knee joint macrophages was monitored by electron microscopy and intracellular accumulation of cyclic adenosine monophosphate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MSU crystals produced a knee joint inflammation that was time dependent and was characterized by cell influx and cytokine release that was sensitive to treatment with classic anti\u2010arthritic drugs (indomethacin, colchicine, dexamethasone). Local, but not systemic, ACTH had an antiinflammatory effect in normal rats, a dose that did not alter circulating corticosterone (5 \u03bcg). This treatment was also effective in adrenalectomized rats. Rat knee joint macrophages expressed functional MC3\u2010R. The MC3\u2010R antagonist (SHU9119, 10 \u03bcg) blocked ACTH antiinflammatory actions, whereas antiinflammatory activity was retained with a selective MC3\u2010R agonist (\u03b3<jats:sub>2<\/jats:sub>\u2010melanocyte\u2013stimulating hormone).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This research provides evidence for a separate mechanism of action of ACTH in experimental gouty arthritis and points to a novel antiinflammatory target (selective agonists at MC3\u2010R) for clinical management of human gouty arthritis and possibly other chronic inflammatory conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10526","type":"journal-article","created":{"date-parts":[[2002,10,17]],"date-time":"2002-10-17T19:54:35Z","timestamp":1034884475000},"page":"2765-2775","source":"Crossref","is-referenced-by-count":149,"title":["Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis"],"prefix":"10.1002","volume":"46","author":[{"given":"Stephen J.","family":"Getting","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Christian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick J.","family":"Flower","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,10,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-56-5-711"},{"key":"e_1_2_6_3_2","first-page":"533","article-title":"Synovial fluid crystals","volume":"48","author":"Dieppe PA","year":"1979","journal-title":"QJM"},{"key":"e_1_2_6_4_2","first-page":"1064","article-title":"Arthritic diseases: melanocortin type 3 receptor agonists as potential therapeutics","volume":"2","author":"Getting SJ","year":"2001","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_6_5_2","first-page":"977","volume-title":"Inflammation: basic principles and clinical correlates","author":"Terkeltaub R","year":"1992"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780321114"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780340716"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115142"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1992.tb01516.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-0172(98)80028-0"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0025-6196(24)00526-3","article-title":"The effect of the adrenal cortex (17\u2010hydroxy\u201011\u2010dehydrocortisone: compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis: preliminary report","volume":"24","author":"Hench PS","year":"1949","journal-title":"Proc Staff Meet Mayo Clin"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310618"},{"key":"e_1_2_6_13_2","first-page":"696","article-title":"ACTH revisited: effective treatment for acute crystal induced synovitis in patients with multiple medical problems","volume":"21","author":"Ritter J","year":"1994","journal-title":"J Rheumatol"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199407000-00013"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(82)90098-5"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01009-8"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00298-8"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1159\/000097281"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.2000.0725"},{"key":"e_1_2_6_20_2","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.4049\/jimmunol.162.12.7446","article-title":"POMC gene\u2010derived peptides activate melanocortin type 3 receptor on murine macrophages, suppress cytokine release, and inhibit neutrophil migration in acute experimental inflammation","volume":"162","author":"Getting SJ","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_6_21_2","first-page":"19","article-title":"Melanocortin receptor type 3 as a novel target for anti\u2010inflammatory therapy","volume":"13","author":"Getting SJ","year":"2000","journal-title":"Drugs News & Perspect"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.69.1.98"},{"key":"e_1_2_6_23_2","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.4049\/jimmunol.152.11.5485","article-title":"Crystal\u2010induced neutrophil activation. 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