Adipocytokine profile, cytokine levels and foxp3 expression in multiple sclerosis: a possible link to susceptibility and clinical course of disease (original) (raw)
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Neurologia i Neurochirurgia Polska, 2012
FoxP3 (p < 0,001) by³y znamiennie mniejsze u chorych na RRMS. Stwierdzono ujemn¹ korelacjê pomiêdzy stê¿eniem leptyny a MFC dla czynnika transkrypcyjnego FoxP3 w limfocytach nTreg u chorych na RRMS (r =-0,7; p < 0,05). Wnioski: Prozapalny profil adipocytokin i zmniejszenie odsetka limfocytów nTreg sugeruje ich udzia³ w przebiegu reakcji zapalnej u chorych na RRMS niezale¿nie od terapii kortykosteroidami. Korelacja pomiêdzy stê¿eniem leptyny i wskaŸnikiem MFC dla czynnika transkrypcyjnego FoxP3 w limfocytach nTreg u chorych na RRMS wskazuje na ha muj¹cy wp³yw leptyny na jego ekspresjê.
Obesity worsens central inflammation and disability in multiple sclerosis
Multiple Sclerosis Journal, 2019
Background: Previous studies evidenced a link between metabolic dysregulation, inflammation, and neurodegeneration in multiple sclerosis (MS). Objectives: To explore whether increased adipocyte mass expressed as body mass index (BMI) and increased serum lipids influence cerebrospinal fluid (CSF) inflammation and disease severity. Methods: In this cross-sectional study, 140 consecutive relapsing-remitting (RR)-MS patients underwent clinical assessment, BMI evaluation, magnetic resonance imaging scan, and blood and CSF collection before any specific drug treatment. The CSF levels of the following cytokines, adipocytokines, and inflammatory factors were measured: interleukin (IL)-6, IL-13, granulocyte macrophage colony-stimulating factor, leptin, ghrelin, osteoprotegerin, osteopontin, plasminogen activator inhibitor-1, resistin, and Annexin A1. Serum levels of triglycerides, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were assessed. Results: A positive corr...
European Journal of Neurology, 2010
Background and purpose: The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS. Methods: Plasma samples were collected from twelve twins and CSF samples from four twins discordant for MS. The concentrations of interleukine (IL)-6, adiponectin, adipsin and leptin in plasma and CSF samples were determined by enzyme immuno assay. Results: A significant difference was seen in the adipocytokine levels in CSF samples. Twins with MS had higher concentrations of adiponectin (P = 0.039) and adipsin (P = 0.039), than their asymptomatic co-twins. Conclusion: As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in MS.
Adipokines as Immune Cell Modulators in Multiple Sclerosis
International Journal of Molecular Sciences, 2021
Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine functi...
Multiple Sclerosis and Obesity: Possible Roles of Adipokines
Mediators of Inflammation, 2016
Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we conc...
Adiponectin profile at baseline is correlated to progression and severity of multiple sclerosis
European Journal of Neurology, 2018
Background and purpose: Adiponectin is a relevant cytokine linking energy metabolism and immune system. After being assembled, adiponectin circulates as oligomers of different molecular weight, LMW, MMW and HMW. These latter have the most potent biological effects. Multiple Sclerosis (MS) is an autoimmune disease of human central nervous system. The aim of this study was to characterize the expression levels of both total Adiponectin and its oligomerization state in the serum from 99 MS patients at the baseline (i.e. not influenced by therapies); we also investigated the potential relationships between Adiponectin and disease progression and severity. Methods: Adiponectin was quantified and visualized by ELISA. Western blotting and FPLC. During the follow up (3.6 years, ± 2.20), the patients were evaluated using total ARR and EDSS. Results: total Adiponectin is statistically higher in MS patients compared to matched controls (12.18 μg/mL vs 10.02 μg/mL, p=0.001). Interestingly, Adiponectin oligomerization state is altered in MS, with an increase of HMW oligomers. In addition, MS patients with higher levels of Adiponectin at baseline have significantly higher risk of progression and severity (MSSS, 3.84 vs 2.44, p=0.001). No statistically difference in Adiponectin expression was found between active and inactive MS patients and among the different forms of disease.
Molecular Neurobiology, 2021
Adiponectin exerts relevant actions in immunity and is modulated in several disorders, such as multiple sclerosis (MS). In this study, we characterized adiponectin expression and profiles in cerebrospinal fluid (CSF) from MS patients to investigate its potential relationship with the severity and progression of the disease. Total adiponectin in CSF was measured by ELISA in 66 unrelated CSF MS patients and compared with 24 age- and sex-matched controls. Adiponectin oligomer profiles were analysed by Western blotting and FPLC chromatography. Total CSF adiponectin was significantly increased in MS patients compared with controls (9.91 ng/mL vs 6.02 ng/mL) (p
European Journal of Immunology, 2013
Multiple Sclerosis (MS) is a presumed autoimmune disease directed against central nervous system (CNS) myelin, in which diet and obesity are implicated as risk factors. Immune responses can be influenced by molecules produced by fat cells, called adipokines. Adiponectin is an adipokine with anti-inflammatory effects. We tested the hypothesis that adiponectin has a protective role in the experimental autoimmune encephalomyelitis (EAE) model for MS, that can be induced by immunization with myelin antigens or transfer of myelin-specific T lymphocytes. Adiponectin deficient (ADPKO) mice developed worse EAE with greater CNS inflammation, demyelination and axon injury. Lymphocytes from myelin-immunized ADP KO mice proliferated more, produced higher amounts of IFNγ, IL-17, TNFα, IL-6 and transferred more severe EAE than wild type (WT) lymphocytes. At EAE peak, the spleen and CNS of ADPKO had fewer Tregulatory cells (Tregs) than WT mice and during EAE recovery, Foxp3, IL-10 and TGFβ CNS expression levels were reduced in ADPKO compared to WT mice. Treatment with globular adiponectin (gADP) in vivo ameliorated EAE, and was associated with an increase in Tregs. These data indicate that adiponectin is an important regulator of T cell functions during EAE, suggesting a new avenue of investigation for MS treatment.
Frontiers in Neuroscience, 2020
Adapted exercise is an effective non-pharmacological tool to improve functional, cognitive, and psychological parameters in multiple sclerosis (MS), in association with increased quality of life (QoL) and decreased disease severity. Adipose tissue, through the production of different adipokines, is involved in regulating energy metabolism and inflammation. Adiponectin, increased in MS, circulates as oligomers of low (LMW), medium (MMW), and high molecular weight (HMW), the latter mediating the main biological effects. The aim of study was to evaluate the effects of 4 months training at moderate intensity [65% heart rate reserve (HRR)] on BMI, adiponectin, and QoL in a volunteer with secondary progressive MS. The parameters were evaluated before (T0), after 4 months training (T1), and 6 months after the end of training (T2); total serum adiponectin and its oligomeric profile were evaluated. We found a reduction in BMI (−0.9%) and FAT (−2.6%), an improvement in perceived QoL and a red...