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Int. J. Mol. Sci. 2015, 16(8), 18683-18713; doi:10.3390/ijms160818683

Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies

1
Neuromuscular Reference Center, Laboratory for Neuropathology, 10K12E, Ghent University Hospital, 9000 Ghent, Belgium
2
Department of Neurology, University Medical Centre, Göttingen University, 37075 Göttingen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Kamal D. Moudgil
Received: 16 June 2015 / Revised: 13 July 2015 / Accepted: 15 July 2015 / Published: 11 August 2015
(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
View Full-Text   |   Download PDF [777 KB, uploaded 11 August 2015]   |  

Abstract

The idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of chronic disorders that include dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). They represent distinct pathological entities that, most often, share predominant inflammation in muscle tissue. Many of the immunopathogenic processes behind the IIM remain poorly understood, but the crucial role of cytokines as essential regulators of the intramuscular build-up of inflammation is undisputed. This review describes the extensive cytokine network within IIM muscle, characterized by strong expression of Tumor Necrosis Factors (TNFα, LTβ, BAFF), Interferons (IFNα/β/γ), Interleukins (IL-1/6/12/15/18/23) and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21). Current therapeutic strategies and the exploration of potential disease modifying agents based on manipulation of the cytokine network are provided. Reported responses to anti-TNFα treatment in IIM are conflicting and new onset DM/PM has been described after administration of anti-TNFα agents to treat other diseases, pointing to the complex effects of TNFα neutralization. Treatment with anti-IFNα has been shown to suppress the IFN type 1 gene signature in DM/PM patients and improve muscle strength. Beneficial effects of anti-IL-1 and anti-IL-6 therapy have also been reported. Cytokine profiling in IIM aids the development of therapeutic strategies and provides approaches to subtype patients for treatment outcome prediction. View Full-Text
Keywords: anakinra; avonex; cytokine; dermatomyositis; etanercept; inflammatory myopathy; infliximab; sifalimumab; tocilizumab; tumor necrosis factor α anakinra; avonex; cytokine; dermatomyositis; etanercept; inflammatory myopathy; infliximab; sifalimumab; tocilizumab; tumor necrosis factor α
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

De Paepe, B.; Zschüntzsch, J. Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies. Int. J. Mol. Sci. 2015, 16, 18683-18713.

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