Evaluation of the relationship between leptin, resistin, adiponectin and natural regulatory T cells in relapsing-remitting multiple sclerosis (original) (raw)
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Background: Adipocytokines 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 Creactive protein (hs-CRP). Methods: A total of 391 subjects including 200 healthy controls and 191 MS patients were recruited for this casecontrol 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). Results: A 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. Conclusions: Our 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.
Journal of Neuroimmunology, 2007
In this study we observed higher serum leptin levels in relapsing-remitting multiple sclerosis (RRMS) patients during remission than in controls. The expression of leptin receptor (ObR) was higher in CD8+ T cells and monocytes from RRMS patients in relapse than in patients in remission and in controls. Relapsing patients showed high levels of pSTAT3 and low expression of SOCS3 and leptin administration induced an up-regulation of pSTAT3 only in monocytes from patients in relapse. Our data suggest that ObR may be involved in the development of clinical relapses in RRMS patients and suggest a rationale for potential targeting of the leptin axis during MS.
Proceedings of the National Academy of Sciences, 2005
We analyzed the serum and cerebrospinal fluid (CSF) leptin secretion and the interaction between serum leptin and CD4 + CD25 + regulatory T cells (T Regs ) in naïve-to-therapy relapsing-remitting multiple sclerosis (RRMS) patients. Leptin production was significantly increased in both serum and CSF of RRMS patients and correlated with IFN-γ secretion in the CSF. T cell lines against human myelin basic protein (hMBP) produced immunoreactive leptin and up-regulated the expression of the leptin receptor (ObR) after activation with hMBP. Treatment with either anti-leptin or anti-leptin-receptor neutralizing antibodies inhibited in vitro proliferation in response to hMBP. Interestingly, in the RRMS patients, an inverse correlation between serum leptin and percentage of circulating T Regs was also observed. To better analyze the finding, we enumerated T Regs in leptin-deficient ( ob / ob ) and leptin-receptor-deficient ( db / db ) mice and observed the significant increase in T Regs . Mor...
Journal of Clinical Immunology, 2000
Leptin, a hormone synthesized mainly by adipocytes, can modulate the immune response and seems to be involved in the induction of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). However, the possible role of leptin in MS pathogenesis has not yet been elucidated. In this study we investigated the effect of leptin on cytokine production by peripheral blood mononuclear cells (PBMCs) of MS patients (either in the acute or in the stable phase of the disease) and healthy controls. We also analyzed leptin effects on cytokine production by monocytes in relapsing MS patients. Our data showed that leptin induced tumor necrosis factor-alpha, interleukin-6, and interleukin-10 production by PBMCs of patients in an acute phase of disease but not in patients in a stable phase or in healthy controls. Moreover, we found no effect of leptin in monocytes from relapsing MS patients. Therefore we conclude that leptin may modulate the MS inflammatory process during relapses.
Journal of Autoimmunity, 2004
Leptin is synthesized by adipocytes to regulate appetite. Leptin has also been implicated in the pathogenesis of multiple sclerosis (MS) leading to speculation about a beneficial effect of fasting to autoimmune patients. We measured plasma leptin and its soluble receptor (OB-Rs) in 52 MS patients and 50 controls. We also cultured MS and control peripheral blood mononuclear cells (PBMC), T-cells and monocytes G recombinant leptin (rleptin), to assess leptin's direct effect on pro-and anti-inflammatory cytokine secretion. We found similar leptin and OB-Rs plasma levels between patients and controls. Untreated patients in the acute phase or in remission, or patients treated with methylprednisolone, had lower leptin levels than patients in the acute phase or in remission receiving IFN-b. OB-Rs levels were low in patients refractory to IFN-b but higher in patients receiving methylprednisolone or patients in remission receiving IFN-b. PBMC from untreated patients in the acute phase, secreted spontaneously IFN-g, TNF-a and IL-10. IFN-g was contributed by T-cells, TNF-a and IL-10 primarily by monocytes and to a lesser extent by T-cells. The overall effect of rleptin on PBMC was a net increase in IL-10 production and a net reduction in IFN-g production. These results do not warrant a beneficial effect of fasting to MS patients.
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.
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.
Leptin as a metabolic link to multiple sclerosis
Nature Reviews Neurology, 2010
Clinical and experimental data, together with epidemiological studies, have suggested that the pathogenesis of multiple sclerosis (MS) might involve factors that link the immune system with metabolic status. Moreover, recent research has shown that leptin, the adipocyte-derived hormone that controls food intake and metabolism, can promote experimental autoimmune encephalomyelitis, an animal model of MS. In patients with MS, the association of leptin with disease activity has been dissected at the molecular level, providing new mechanistic explanations for the role of this hormone in MS. Here, we review the intricate relationship between leptin and other metabolic modulators within a framework that incorporates the latest advances linking the CNS, immune tolerance and metabolic status. We also consider the translational implications of these new findings for improved management of MS.