Gout is a chronic inflammatory disease where high levels of interleukin 8 (CXCL8), MRP8/14 and an altered proteome associate with diabetes and cardiovascular disease

Abstract

OBJECTIVES: The frequent association with the metabolic syndrome and cardiovascular disease (CVD) suggest a systemic component in gout. Our objective was to study whether circulating pro-inflammatory cytokines are associated with comorbidities in gout patients. METHODS: We studied 330 gout patients from three independent cohorts and compared those with 144 healthy individuals and 276 disease controls. Circulating levels of IL-8 (CXCL8), IL-1b, IL-6, IL-10, IL-12, TNF-a were measured, after which proteome-wide analysis was performed in a selection of samples to determine possible prognostic proteins for the development of comorbidities. Replication analysis was performed specifically for MRP8/14. RESULTS: Compared to healthy and disease controls, patients with gouty arthritis (n=48) had significantly higher mean levels of CXCL8 (P < 0.001) whereas other cytokines were almost undetectable. Similarly, patients with intercritical gout also showed high levels of CXCL8. CXCL8 was independently associated (P<0.0001) with diabetes in intercritical gout patients. Proteome-wide analysis in gouty arthritis (n=18) and intercritical gout (n=39) revealed MRP8/14 as the protein with the greatest differential expression and correlation with CXCL8 (R(2) 0.49, P<0.001), which was replicated in an independent cohort. The proteome of gout patients with high CXCL8 was associated with diabetes (OR, 95% CI; 16.5, 2.8-96.6) and CVD (OR, 95% CI; 3.9, 1.0-15.3). CONCLUSIONS: Circulating levels of CXCL8 levels are increased during both the arthritis and intercritical phases of gout, and coincides with a specific circulating proteome that is associated with diabetes and CVD risk. Further research focussed on the role CXCL8 and MRP8/14 in patients with gout is warranted. This article is protected by copyright.