Open Access
Michalak et al., J Neurol Neurophysiol 2014, S12
DOI: 10.4172/2155-9562.S12-005
Open Access
J Neurol Neurophysiol ISSN: 2155-9562 JNN, an open access journal
Neurodegenerative Diseases:
Symptoms and Therapeutics
The Effect of Methylprednisolone, Interferon Beta and Glatiramer Acetate
Treatment on the Levels of Leptin, Adiponectin and Resistin in Multiple
Sclerosis Patients
Slawomir Michalak
1,2
*, Lukasz Jernas
3
*, Ewa Wysocka
4
, Krystyna Osztynowicz
1
, Elzbieta Tokarz-Kupczyk
3
, Halina Wygladalska-Jernas
3
and Wojciech Kozubski
3
1
Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, 60-355 Poznan, Przybyszewskiego str. 49, Poland
2
Neuroimmunological Unit, Polish Academy of Sciences, 60-355 Poznan, Przybyszewskiego str. 49, Poland
3
Department of Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Przybyszewskiego str. 49, Poland
4
Department of Clinical Biochemistry and Laboratory Medicine, Chair of Chemistry and Clinical Biochemistry, Poznan University of Medical Sciences, Poland
*Corresponding author: Slawomir Michalak, Department of Neurochemistry
and Neuropathology, Poznan University of Medical Sciences, 60-355 Poznan,
Przybyszewskiego str. 49, Poland, Tel: +48 61 8691 443; Fax: +48 61 8691 444;
E-mail: swami622@gmail.com
Received December 21, 2013; Accepted February 19, 2014; Published February
27, 2014
Citation: Michalak S, Jernas L, Wysocka E, Osztynowicz K, Kupczyk ET, et al.
(2014) The Effect of Methylprednisolone, Interferon Beta and Glatiramer Acetate
Treatment on the Levels of Leptin, Adiponectin and Resistin in Multiple Sclerosis
Patients. J Neurol Neurophysiol S12: 005. doi:10.4172/2155-9562.S12-005
Copyright: © 2014 Michalak S, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Keywords: Leptin; Resistin; Adiponectin; Multiple sclerosis;
Methylprednisolone; Interferon-1b; Glatiramer acetate
Introduction
Adipocytokines are cytokine-like mediators produced by adipose
tissue and are involved in infammation, immune response, and
metabolism. Leptin, adiponectin, and resistin belong to the most
abundant family of adipocytokines that link adipose tissue function
with infammatory and autoimmune processes [1]. Leptin is recognized
as an immunendocrine mediator. On the one hand, it controls the
homeostatic balance between food intake and energy expenditure, its
concentration increases during fat accumulation and decreases during
fasting. Te concentration of leptin in the sera of obese individuals
is increased, indicating these individuals have leptin-resistance [2].
Additionally, its reduction contributes to insulin resistance in animal
models [3]. On the other hand, leptin acts as a pro-infammatory
adipocytokine by stimulating the production of interleukin 6 (IL-6),
tumor necrosis factor alpha (TNF-α) and interleukin 12 (IL-12) in
monocytes and macrophages [4], and inhibiting the production of anti-
infammatory cytokines, including interleukin 4 (IL-4), in CD4+ T cells
[5]. Resistin is also a pro-infammatory adipocytokine that is produced
by adipocytes, macrophages, and mononuclear cells. It stimulates
the production of pro-infammatory cytokines like TNF-α and IL-12
[6]. Moreover, resistin regulates the immune response by infuencing
regulatory T cells. It inhibits the expression of interferon regulatory
factor (IRF)-1 and related cytokines, IL-6, interleukin 23p19 (IL-23p19)
and interleukin 12p40 (IL-12p40) in dendritic cells, which also mediate
the upregulation of Forkhead box P3 (FoxP3) expression in CD4+
T by resistin [7]. Te decreased insulin-mediated downregulation
of gluconeogenesis and increased glycogenolysis [8] and decrease in
insulin-stimulated phosphorylation of key regulatory liver enzymes,
all metabolic efects caused by resistin [9], leads to hepatic insulin
resistance. In contrast to leptin and resistin, adiponectin acts as an anti-
infammatory adipocytokine [1], and also promotes insulin sensitivity
Abstract
Objective: Adipocytokines are cytokine-like mediators that link adipose tissue function with infammatory and
autoimmune processes, and have a suggested role in the pathogenesis of multiple sclerosis (MS). The aim of this
study was to analyze the effects of methylprednisolone, interferon-1b (INF) and glatiramer acetate (GA) on leptin,
resistin, and adiponectin concentrations in relapsing-remitting MS (RRMS) patients.
Methods: The study included 154 RRMS patients who were hospitalized in the Department of Neurology, Poznan
University of Medical Sciences. The comparison group included 31 patients with myasthenia gravis (MG) and 39
healthy controls. Serum levels of leptin, adiponectin, and resistin were evaluated before treatment initiation. In the
RRMS patients treated with methylprednisolone, adipocytokine evaluation was performed one day after the therapy.
Patients treated with INF or GA were evaluated at 1 month and 6 months. Routine neurological examination and
expanded disability status scale (EDSS) scoring were performed, and MRI scans were analyzed for the localization
of demyelinating plaques. Body mass index, glycemia, and insulin levels were evaluated and homeostatic model
assessment insulin resistance index (HOMA-IR) was calculated.
Results: Adiponectin and resistin levels in RRMS and MG patients were increased compared to controls, but
adiponectin levels were lower in RRMS than MG patients. Intravenous methylprednisolone in RRMS with relapse
caused an elevation of leptin concentration. INF treatment caused a signifcant, time-dependent effect on resistin
concentration. GA administration infuenced only resistin concentration as a long-term effect. No relationship between
adipocytokines and metabolic status or insulin resistance was found.
Conclusions: We identifed resistin as the most important adipocytokine associated with RRMS. Its concentrations
are reduced by frst line immunomodulatory treatment, which produces a milieu of benefcial infammatory and
metabolic processes. On the other hand, the routine treatment of MS relapses with methylprednisolone induces
harmful metabolic and infammatory effects that may be mediated by elevated leptin levels.
Journal of Neurology & Neurophysiology
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ISSN: 2155-9562
Research Article