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

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, s...

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Autores principales: De Paepe, Boel, Zschüntzsch, Jana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581266/
https://www.ncbi.nlm.nih.gov/pubmed/26270565
http://dx.doi.org/10.3390/ijms160818683
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author De Paepe, Boel
Zschüntzsch, Jana
author_facet De Paepe, Boel
Zschüntzsch, Jana
author_sort De Paepe, Boel
collection PubMed
description 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.
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spelling pubmed-45812662015-09-28 Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies De Paepe, Boel Zschüntzsch, Jana Int J Mol Sci Review 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. MDPI 2015-08-11 /pmc/articles/PMC4581266/ /pubmed/26270565 http://dx.doi.org/10.3390/ijms160818683 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
De Paepe, Boel
Zschüntzsch, Jana
Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
title Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
title_full Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
title_fullStr Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
title_full_unstemmed Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
title_short Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
title_sort scanning for therapeutic targets within the cytokine network of idiopathic inflammatory myopathies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581266/
https://www.ncbi.nlm.nih.gov/pubmed/26270565
http://dx.doi.org/10.3390/ijms160818683
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