{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:53:32Z","timestamp":1790844812004,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T00:00:00Z","timestamp":1246233600000},"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":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Kawasaki disease (KD) is a multisystem vasculitis affecting children and is characterized by immune activation in the acute stage of disease. Systemic inflammation eventually subsides, although coronary arteritis persists, resulting in aneurysm formation. KD is the leading cause of acquired heart disease among children in North America. Accepted treatment guidelines include high\u2010dose intravenous immunoglobulin (IVIG) and aspirin in the acute phase. Although this therapy is effective, the cellular and molecular mechanisms involved are not clear. The aim of this study was to examine the effect of IVIG and salicylate at each stage of disease development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a murine model of KD, we established and validated several in vitro techniques to reflect 3 key steps involved in disease pathogenesis, as follows: thymidine incorporation to evaluate T cell activation, enzyme\u2010linked immunosorbent assay to measure tumor necrosis factor \u03b1 (TNF\u03b1) production, and real\u2010time polymerase chain reaction to examine TNF\u03b1\u2010mediated expression of matrix metalloproteinase 9 (MMP\u20109).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At therapeutic concentrations, IVIG, but not salicylate, effectively reduced the immune response leading to TNF\u03b1 expression. Unexpectedly, pharmacologic doses of salicylate were not able to inhibit TNF\u03b1 production and in fact enhanced its production. Neither drug directly regulated MMP\u20109 expression but did so only indirectly via modulating TNF\u03b1. TNF\u03b1 activity was a prerequisite for local expression of MMP\u20109 at the coronary artery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Therapeutic concentrations of IVIG and salicylate differentially modulate the expression of TNF\u03b1 and its downstream effects. Further dissection of the biologic effects of aspirin in acute KD is necessary for the rational design of therapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24660","type":"journal-article","created":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T15:05:41Z","timestamp":1246287941000},"page":"2131-2141","source":"Crossref","is-referenced-by-count":46,"title":["Intravenous immunoglobulin and salicylate differentially modulate pathogenic processes leading to vascular damage in a model of Kawasaki disease"],"prefix":"10.1002","volume":"60","author":[{"given":"Andrew C.","family":"Lau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang T.","family":"Duong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rae S. 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