Abstract

IntroductionThe purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity.MethodsSerum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed.ResultsIn patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes.ConclusionsThe results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies.

Highlights

  • The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity

  • Resistin is up-regulated by inflammatory mediators in peripheral blood mononuclear cells (PBMC) and induces the expression of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-a, angiogenic factors and extracellular matrix metalloproteinases, suggesting a broad contribution to many pathological conditions [4,5,6,7,8,9,10,11]

  • In patients with DM, serum resistin levels significantly correlated with myositis disease activity assessment visual analogue scales (MYOACT) score (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with C-reactive protein (CRP) levels (r = 0.447, P = 0.067)

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Summary

Introduction

The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. The inflammatory myopathies are a group of acquired skeletal muscle diseases that include polymyositis (PM), dermatomyositis (DM), inclusion body myositis, and overlap and cancer-associated myositis. An autoimmune origin of inflammatory myopathies is supported by their invade non-necrotic muscle fibres [1]. The pathogenesis of inflammatory myopathies has not yet been completely elucidated, but several cytokines and chemokines produced by immune cells and myocytes have already been shown to be involved in the process of muscle tissue damage during myositis [reviewed in [2]]. Resistin was found in adipocytes to induce insulin resistance in mice. It has been associated with several metabolic disorders and with cancer, inflammatory and immunemediated diseases [3]. Resistin is up-regulated by inflammatory mediators in peripheral blood mononuclear cells (PBMC) and induces the expression of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and tumour necrosis factor (TNF)-a, angiogenic factors and extracellular matrix metalloproteinases, suggesting a broad contribution to many pathological conditions [4,5,6,7,8,9,10,11]

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