Abstract
BackgroundAdipocytokines may be involved in multiple sclerosis (MS) as well as other autoimmune and inflammatory-related diseases. This study aims to compare levels of resistin, visfatin and leptin in three subgroups of MS patients with healthy subjects and also to study their relationship with Foxp3 expression and levels of several pro-inflammatory mediators such as interleukine-1 β(IL-1 β),tumor necrosis factor-α (TNF-α) and human sensitive C-reactive protein (hs-CRP).MethodsA total of 391 subjects including 200 healthy controls and 191 MS patients were recruited for this case-control study. Circulating adipocytokines and inflammatory mediators were measured using immunoassay methods. Foxp3 gene expression in peripheral blood mononuclear cells (PBMC) was determined by quantitative real-time PCR. Fat tissue mass was evaluated by using dual energy X-ray absorptiometery (DEXA).ResultsA significant difference was observed in levels of inflammatory mediators, adipocytokines, Foxp3 gene expression and adipose tissue mass between MS patients and healthy controls. All adipocytokines were positively correlated with levels of inflammatory mediators and negatively correlated with Foxp3 expression in MS patients. In controls, there were positive correlations between circulating leptin and resistin with TNF-α and IL-1β in subgroup analysis, the highest levels of TNF-α, IL-1β, hs-CRP, resistin and leptin were observed in primary progressive-MS (PP-MS) patients. Also, expression of Foxp3 and levels of visfatin in relapsing remitting-MS(RR-MS) patients were higher compared with the other subgroups.ConclusionsOur findings suggest the potential role of adipocytokines in pathogenesis and severity of MS. Notably, the relationship of adipocytokines levels with inflammatory cytokines as well as clinical features of MS could be considerable in translational medicine and biomarker studies.
Highlights
There was no significant difference between the two study groups regarding age, sex, height, weight and body mass index, adipose tissue mass percentage significantly decreased in patient group as compared with control subjects (18.26±8.78 vs. 22.57±9.26, p
The first observation of this study was a significant elevation in circulating resistin,leptin and visfatin as well as proinflammatory mediators in multiple sclerosis (MS) patients that was accompanied by markedly decrease in mRNA Foxp3 expression of T cells
These findings are in accordance with our previous investigations and several other studies indicating an elevation in circulating resistin, leptin, visfatin, tumor necrosis factor-α (TNF-α),IL-1β and human sensitive Creactive protein (hs-CRP) as well as decrease in mRNA Foxp3 expression of T cells in MS patients [6,12,17,18]
Summary
Multiple sclerosis (MS), the most common cause of neurological disability in young people and middle-aged adults, affects up to 2 million people worldwide[1].Importantly, it represents a considerable heterogeneity regarding clinical course, immunological features, pathogenesis and imaging appearances[2].the etiology of MS is not fully understood, available evidence indicates that immune system plays an important role in pathogenesis of MS [3,4,5].Increased production of Th1 cell-derived cytokine (IFN-γ, IL-12 and TNF-α) and Th17 cell-derived ones (IL-17 and IL-6), and reduced number and activity of regulatory T (Treg) cells appears to play an important role in this regard [4,6,7,8].Notably, Treg cells by expression of the forkhead transcription factor (Foxp3) have a vital role in promoting and maintaining of self-tolerance, thereby preventing chronic inflammatory diseases and autoimmune diseases [9,10,11].Several studies have demonstrated that alternation in Treg cell function and amount of pro inflammatory cytokines, determines disease susceptibility and/or affects relapse and remission phase in MS[12,13,14,15]. Multiple sclerosis (MS), the most common cause of neurological disability in young people and middle-aged adults, affects up to 2 million people worldwide[1]. It represents a considerable heterogeneity regarding clinical course, immunological features, pathogenesis and imaging appearances[2]. This study aims to compare levels of resistin, visfatin and leptin in three subgroups of MS patients with healthy subjects and to study their relationship with Foxp expression and levels of several pro-inflammatory mediators such as interleukine-1 β(IL-1 β),tumor necrosis factor-α (TNF-α) and human sensitive Creactive protein (hs-CRP). Results: A significant difference was observed in levels of inflammatory mediators, adipocytokines, Foxp gene expression and adipose tissue mass between MS patients and healthy controls. The relationship of adipocytokines levels with inflammatory cytokines as well as clinical features of MS could be considerable in translational medicine and biomarker studies
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