Increased Metallothionein-1 associated with gout activity and tophi

Abstract Introduction：Gout is a chronic self-limiting inflammatory arthritis. The mechanism for the spontaneous rapid resolution of inflammation in acute gout was not yet to be elucidated. Metallothionein-1(MT-1) belongs to the metallothionein family, it has been reported to increase in rheumatoid arthritis (RA) and osteoarthritis (OA), and attenuate the inflammation and pathology of the diseases, however the expression of MT-1 in gout and the correlation with the disease activity are still unclear. The present study aims to detect the level of MT-1 in gout patients, and to explore its correlation with disease activity, complication, clinical indexes and inflammatory cytokines.Methods：The expressions of MT-1 mRNAs in PBMCs and serum MT-1 levels in gout patients were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The correlations between MT-1 and clinical indexes or inflammatory mediators in serum of gout were analyzed by Spearman correlation test.Results：Compared to healthy controls (HCs), active gout patients showed higher levels of MT-1 mRNA in PBMCs and protein in serum, especially in active gout patients with tophi. No significant difference in serum MT-1 levels was observed among the inactive gout patients, HCs and hyperuricemia patients without gout, and also no significant difference was found between kidney damage gout patients and HCs. Compared to HCs, serum IL-1β, IL-6 and IL-8 levels were significant elevated in active gout patients, especially in active gout patients with tophi. Serum MT-1 were positively correlated with CRP, as well as with IL-1β, IL-6 and IL-18, but not correlated with urid acid (UA), ESR and CREA in gout patients. Conclusion：MT-1 was up-regulated in active gout patients, especially in active gout patients with tophi, and positively associated with CRP, as well as with proinflammatory cytokine IL-1β, IL-6 and IL-8. Given that MT-1 has anti-inflammatory, anti-oxidative stress capacity in chronic noninfectious inflammatory diseases, thus, elevated MT-1 in active gout patients may play as an immune mediator to suppress the inflammatory response in acute gout episode.