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Combinatorial Effect of Metformin and Lovastatin Impedes T-cell Autoimmunity and Neurodegeneration in Experimental Autoimmune Encephalomyelitis | OMICS International | Abstract
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
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Research Article

Combinatorial Effect of Metformin and Lovastatin Impedes T-cell Autoimmunity and Neurodegeneration in Experimental Autoimmune Encephalomyelitis

Ajaib S Paintlia#, Sarumathi Mohan# and Inderjit Singh*
Darby Children’s Research Institute, Department of Pediatrics, Medical University of South Carolina Charleston, South Carolina 29425, USA
#These authors contributed equally to this study
Corresponding Author : Inderjit Singh, PhD
Medical University of South Carolina
Department of Pediatrics
173 Ashley Avenue
Charleston, SC 29425, USA
Tel: (843) 792-7542
Fax: (843) 792-7130
E-mail: [email protected]
Received June 03, 2013; Accepted June 24, 2013; Published June 30, 2013
Citation: Paintlia AS, Mohan S, Singh I (2013) Combinatorial Effect of Metformin and Lovastatin Impedes T-cell Autoimmunity and Neurodegeneration in Experimental Autoimmune Encephalomyelitis. J Clin Cell Immunol 4:149. doi:10.4172/2155-9899.1000149
Copyright: © 2013 Paintlia AS, 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.
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Abstract

Multiple Sclerosis (MS) is an incurable central nervous system (CNS) demyelinating disease affecting several million people worldwide. Due to the multifactorial and complex pathology of MS, FDA approved drugs often show limited efficacy inpatients. We earlier documented that both lovastatin (cholesterol lowering drug) and metformin (anti-diabetic drug) attenuate experimental autoimmune encephalomyelitis (EAE), a widely used model of MS via different mechanisms of action. Since combination therapy of two or more agents has advantage over monotherapy, we here assessed the therapeutic efficacy of metformin and lovastatin combination in EAE. We found that suboptimal doses of these drugs in combination had additive effect to attenuate established EAE in treated animals than their individual treatments. Histological, immunohistochemistry and western blotting analyses revealed that the observed demyelination and axonal loss as evident from reduced levels of myelin and neurofilament proteins in the spinal cords of EAE animals were attenuated by treatment with these drugs in combination. Accordingly, the observed infiltration of myelin reactive T cells (CD4 and CD8) and macrophages (CD68) as well as the increased expression of their signatory cytokines in the spinal cords of EAE animals were attenuated by this regimen as revealed by enzymelinked immune-sorbent assay and real-time PCR analyses. In the periphery, this regimen biased the class of elicited anti-myelin basic protein immunoglobulins from IgG2a to IgG1 and IgG2b, suggesting a Th1 to Th2 shift which was further supported by the increased expression of their signatory cytokines in EAE animals. Taken together, these data imply that metformin and lovastatin combination attenuates T-cell autoimmunity and neurodegeneration in treated EAE animals thereby suggesting that the oral administration of these FDA approved drugs in combination has potential to limit MS pathogenesis.

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