{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:03:05Z","timestamp":1779883385482,"version":"3.53.1"},"reference-count":31,"publisher":"The Journal of Rheumatology","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>To determine whether monosodium urate (MSU) crystal-induced superoxide production is greater for neutrophils from patients with gout compared to asymptomatic hyperuricemic and healthy controls, and whether neutrophil functions are altered by an MSU crystal-induced inflammatory environment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Neutrophils were purified from the whole blood of study participants, restimulated with 500 mg MSU crystals<jats:italic>ex vivo<\/jats:italic>, and superoxide production measured using the colorimetric dye WST-1. Purified neutrophils were exposed to conditioned media from MSU crystal-activated blood monocyte cultures with and without neutralizing antibodies for interleukin 1\u00df (IL-1\u00df), IL-8 (CXCL8), IL-6, and tumor necrosis factor-\u03b1 (TNF-\u03b1). Neutrophil superoxide production was measured and neutrophil apoptosis and IL-8 production were determined by flow cytometry. Serum samples were collected from participants and analyzed by Lincoplex bead array for IL-1\u00df, IL-8, IL-6, and TNF-\u03b1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Neutrophils from gout and asymptomatic hyperuricemic subjects produced higher levels of MSU crystal-induced superoxide, and a weak trend toward elevated serum cytokines was observed compared to healthy controls. A correlation between serum uric acid and elevated neutrophil superoxide production was also observed. Neutrophils exposed to media from MSU crystal-activated monocytes exhibited enhanced superoxide production to MSU-crystal stimulation, increased IL-8 production, and extended cell survival that was predominantly dependent on IL-8, TNF-\u03b1 and IL-6, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>Neutrophils from gout and asymptomatic hyperuricemic individuals are primed for enhanced MSU crystal-induced superoxide production that may be driven by a subclinical inflammatory cytokine environment combined with hyperuricemia. This inflammatory environment likely contributes to elevated neutrophil IL-8 production and survival in the absence of direct crystal stimulation. Asymptomatic hyperuricemia is not associated with suppressed neutrophil function.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.091080","type":"journal-article","created":{"date-parts":[[2010,4,16]],"date-time":"2010-04-16T02:54:31Z","timestamp":1271386471000},"page":"1228-1235","source":"Crossref","is-referenced-by-count":30,"title":["Differences in MSU-induced Superoxide Responses by Neutrophils from Gout Subjects Compared to Healthy Controls and a Role for Environmental Inflammatory Cytokines and Hyperuricemia in Neutrophil Function and Survival"],"prefix":"10.3899","volume":"37","author":[{"given":"WILLIAM JOHN","family":"MARTIN","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"REBECCA","family":"GRAINGER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANDREW","family":"HARRISON","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JACQUIE L.","family":"HARPER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2010,4,15]]},"reference":[{"key":"2018112909231426000_37.6.1228.1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1084\/jem.124.1.115","article-title":"Crystal-induced inflammation in canine joints II. 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