{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:55:55Z","timestamp":1790762155350,"version":"4.1.0"},"reference-count":24,"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 investigate whether the increased interleukin\u20101\u03b2 (IL\u20101\u03b2) secretion in hyperimmunoglobulinemia D and periodic fever syndrome is due to the accumulation of mevalonate kinase (MK), the substrate of the deficient enzyme, or the lack of its products, the isoprenoid compounds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of lovastatin and farnesol (FOH), geranylgeraniol (GGOH), and mevalonate on peripheral blood mononuclear cells (PBMCs) from 8 patients with MK deficiency and from 13 controls were studied. Lovastatin inhibits isoprenoid biosynthesis by reducing the production of mevalonate. FOH and GGOH restore isoprenoid biosynthesis downstream from MK. Culture supernatants were collected for cytokine analysis 48 hours after stimulation with monoclonal antibodies against CD2 + CD28.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lovastatin induced a 15\u2010fold rise in IL\u20101\u03b2 secretion by normal anti\u2013CD2 + CD28\u2013stimulated cells (<jats:italic>P<\/jats:italic> &lt; 0.001). This effect could be countered by mevalonate and, to a lesser extent, by FOH and GGOH. In the absence of lovastatin, mevalonate did not change IL\u20101\u03b2 secretion. Stimulated MK\u2010deficient cells secreted 9\u2010fold more IL\u20101\u03b2 than control PBMCs (<jats:italic>P<\/jats:italic> &lt; 0.005), rising 2.4\u2010fold in the presence of lovastatin. The effect of lovastatin on IL\u20101\u03b2 secretion was reduced by mevalonate, FOH, and GGOH. Isoprenoid biosynthesis in PBMCs from patients was impaired due to the endogenous MK deficiency. Bypassing this defect with FOH, in the absence of lovastatin, led to a 62% reduction (<jats:italic>P<\/jats:italic> &lt; 0.02) in IL\u20101\u03b2 secretion by these cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this model, shortage of isoprenoid end products contributes to increased IL\u20101\u03b2 secretion by MK\u2010deficient PBMCs, whereas excess mevalonate does not.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10550","type":"journal-article","created":{"date-parts":[[2002,10,17]],"date-time":"2002-10-17T19:54:35Z","timestamp":1034884475000},"page":"2794-2803","source":"Crossref","is-referenced-by-count":141,"title":["Lack of isoprenoid products raises ex vivo interleukin\u20101\u03b2 secretion in hyperimmunoglobulinemia D and periodic fever syndrome"],"prefix":"10.1002","volume":"46","author":[{"given":"Joost","family":"Frenkel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger T.","family":"Rijkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia H. L.","family":"Mandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra W. M.","family":"Buurman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander M.","family":"Houten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J. A.","family":"Wanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans R.","family":"Waterham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wietse","family":"Kuis","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":"10.1097\/00005792-199405000-00002"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra010200"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.12.3586.bloodjournal85123586"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1995.tb01986.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"400","DOI":"10.4049\/jimmunol.157.1.400","article-title":"Unstimulated peripheral blood mononuclear cells from patients with the hyper\u2010IgD syndrome produce cytokines capable of potent induction of C\u2010reactive protein and serum amyloid A in Hep3B cells","volume":"157","author":"Drenth JP","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/9691"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/9696"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42199-0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.91.5.915"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/343425a0"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/82219"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(96)00108-7"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66194-6"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.36.3.325"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00469-5"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.5.2712"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00417-2"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1854"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/40.5.579"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80539-5"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0997-25"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80721-7"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng756"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00124-2"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.10550","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.10550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T07:34:39Z","timestamp":1696664079000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.10550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,10]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2002,10]]}},"alternative-id":["10.1002\/art.10550"],"URL":"https:\/\/doi.org\/10.1002\/art.10550","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,10]]}}}