Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin-8 (CXCL8), Myeloid-Related Protein 8/Myeloid-Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease.

Autor: Kienhorst LB; Rijnstate Hospital, Arnhem, The Netherlands., van Lochem E; Rijnstate Hospital, Arnhem, The Netherlands., Kievit W; Radboud University Medical Center, Nijmegen, The Netherlands., Dalbeth N; University of Auckland, Auckland, New Zealand., Merriman ME; University of Otago, Dunedin, New Zealand., Phipps-Green A; University of Otago, Dunedin, New Zealand., Loof A; Radboud University Medical Center, Nijmegen, The Netherlands., van Heerde W; Radboud University Medical Center, Nijmegen, The Netherlands., Vermeulen S; Radboud University Medical Center, Nijmegen, The Netherlands., Stamp LK; University of Otago, Christchurch, New Zealand., van Koolwijk E; Rijnstate Hospital, Arnhem, The Netherlands., de Graaf J; Radboud University Medical Center, Nijmegen, The Netherlands., Holzinger D; University Hospital Muenster, Muenster, Germany., Roth J; University Hospital Muenster, Muenster, Germany., Janssens HJ; Radboud University Medical Center, Nijmegen, The Netherlands, and Rijnstate Hospital, Arnhem, The Netherlands., Merriman TR; University of Otago, Dunedin, New Zealand., Broen JC; University Medical Center Utrecht, Utrecht, The Netherlands., Janssen M; Rijnstate Hospital, Arnhem, The Netherlands., Radstake TR; University Medical Center Utrecht, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2015 Dec; Vol. 67 (12), pp. 3303-13.
DOI: 10.1002/art.39318
Abstrakt: Objective: The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients.
Methods: We studied 330 gout patients from 3 independent cohorts and compared them with 144 healthy individuals and 276 disease controls. We measured circulating levels of interleukin-8 (IL-8)/CXCL8, IL-1β, IL-6, IL-10, IL-12, and tumor necrosis factor, after which we performed proteome-wide analysis in a selection of samples to identify proteins that were possibly prognostic for the development of comorbidities. Replication analysis was performed specifically for myeloid-related protein 8 (MRP-8)/MRP-14 complex.
Results: Compared to healthy controls and disease control patients, patients with gouty arthritis (n = 48) had significantly higher mean levels of CXCL8 (P < 0.001), while other cytokines were almost undetectable. Similarly, patients with intercritical gout showed high levels of CXCL8. CXCL8 was independently associated with diabetes mellitus in patients with intercritical gout (P < 0.0001). Proteome-wide analysis in gouty arthritis (n = 18) and intercritical gout (n = 39) revealed MRP-8 and MRP-14 as the proteins with the greatest differential expression between low and high levels of CXCL8 and also showed a positive correlation of MRP8/MRP14 complex with CXCL8 levels (R(2)  = 0.49, P < 0.001). These findings were replicated in an independent cohort. The proteome of gout patients with high levels of CXCL8 was associated with diabetes mellitus (odds ratio 16.5 [95% confidence interval 2.8-96.6]) and CVD (odds ratio 3.9 [95% confidence interval 1.0-15.3]).
Conclusion: Circulating levels of CXCL8 are increased during both the acute and intercritical phases of gout, and they coincide with a specific circulating proteome that is associated with risk of diabetes mellitus and CVD. Further research focused on the roles of CXCL8 and MRP8/MRP14 complex in patients with gout is warranted.
(© 2015, American College of Rheumatology.)
Databáze: MEDLINE
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