{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T03:33:49Z","timestamp":1771644829688,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,8,30]],"date-time":"2007-08-30T00:00:00Z","timestamp":1188432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the synthesis, processing, and secretion of interleukin\u20101\u03b2 (IL\u20101\u03b2), as well as the clinical and biologic effects of IL\u20101 blockade, in patients with chronic infantile neurologic, cutaneous, articular (CINCA) syndrome and Muckle\u2010Wells syndrome (MWS), in an effort to understand the molecular mechanisms linking mutations of the <jats:italic>CIAS1<\/jats:italic> gene and IL\u20101\u03b2 hypersecretion, and the underlying response to IL\u20101 receptor antagonist (IL\u20101Ra).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Six patients with CINCA syndrome or MWS were treated with IL\u20101Ra and followed up longitudinally. Monocytes obtained from the patients and from 24 healthy donors were activated with lipopolysaccharide (LPS) for 3 hours, and intracellular and secreted IL\u20101\u03b2 levels were determined by Western blotting and enzyme\u2010linked immunosorbent assay before and after exposure to exogenous ATP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LPS\u2010induced IL\u20101\u03b2 secretion was markedly increased in monocytes from patients with <jats:italic>CIAS1<\/jats:italic> mutations. However, unlike in healthy subjects, secretion of IL\u20101\u03b2 was not induced by exogenous ATP. Treatment with IL\u20101Ra resulted in a dramatic clinical improvement, which was paralleled by an early and strong down\u2010regulation of LPS\u2010induced IL\u20101\u03b2 secretion by the patients' cells in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results showed that the requirements of ATP stimulation for IL\u20101\u03b2 release observed in healthy individuals are bypassed in patients bearing <jats:italic>CIAS1<\/jats:italic> mutations. This indicates that cryopyrin is the direct target of ATP and that the mutations release the protein from the requirement of ATP for activation. In addition, the dramatic amelioration induced by IL\u20101Ra treatment is at least partly due to the strong decrease in IL\u20101\u03b2 secretion that follows the first injections of the antagonist. These findings may have implications for other chronic inflammatory conditions characterized by increased IL\u20101\u03b2.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22842","type":"journal-article","created":{"date-parts":[[2007,8,30]],"date-time":"2007-08-30T19:16:49Z","timestamp":1188501409000},"page":"3138-3148","source":"Crossref","is-referenced-by-count":215,"title":["Pattern of interleukin\u20101\u03b2 secretion in response to lipopolysaccharide and ATP before and after interleukin\u20101 blockade in patients with <i>CIAS1<\/i> mutations"],"prefix":"10.1002","volume":"56","author":[{"given":"Marco","family":"Gattorno","sequence":"first","affiliation":[]},{"given":"Sara","family":"Tassi","sequence":"additional","affiliation":[]},{"given":"Sonia","family":"Carta","sequence":"additional","affiliation":[]},{"given":"Laura","family":"Delfino","sequence":"additional","affiliation":[]},{"given":"Francesca","family":"Ferlito","sequence":"additional","affiliation":[]},{"given":"Maria 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