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Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?

Systemic sclerosis (SS) is a chronic autoimmune disorder, which has both cutaneous and systemic clinical manifestations. The disease pathogenesis includes a triad of manifestations, such as vasculopathy, autoimmunity, and fibrosis. Interleukin-6 (IL-6) has a special role in SS development, both in v...

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Autores principales: Cardoneanu, Anca, Burlui, Alexandra Maria, Macovei, Luana Andreea, Bratoiu, Ioana, Richter, Patricia, Rezus, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869570/
https://www.ncbi.nlm.nih.gov/pubmed/35203527
http://dx.doi.org/10.3390/biomedicines10020318
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author Cardoneanu, Anca
Burlui, Alexandra Maria
Macovei, Luana Andreea
Bratoiu, Ioana
Richter, Patricia
Rezus, Elena
author_facet Cardoneanu, Anca
Burlui, Alexandra Maria
Macovei, Luana Andreea
Bratoiu, Ioana
Richter, Patricia
Rezus, Elena
author_sort Cardoneanu, Anca
collection PubMed
description Systemic sclerosis (SS) is a chronic autoimmune disorder, which has both cutaneous and systemic clinical manifestations. The disease pathogenesis includes a triad of manifestations, such as vasculopathy, autoimmunity, and fibrosis. Interleukin-6 (IL-6) has a special role in SS development, both in vascular damage and in the development of fibrosis. In the early stages, IL-6 participates in vascular endothelial activation and apoptosis, leading to the release of damage-associated molecular patterns (DAMPs), which maintain inflammation and autoimmunity. Moreover, IL-6 plays an important role in the development of fibrotic changes by mediating the transformation of fibroblasts into myofibroblasts. All of these are associated with disabling clinical manifestations, such as skin thickening, pulmonary fibrosis, pulmonary arterial hypertension (PAH), heart failure, and dysphagia. Tocilizumab is a humanized monoclonal antibody that inhibits IL-6 by binding to the specific receptor, thus preventing its proinflammatory and fibrotic actions. Anti-IL-6 therapy with Tocilizumab is a new hope for SS patients, with data from clinical trials supporting the favorable effect, especially on skin and lung damage.
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spelling pubmed-88695702022-02-25 Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6? Cardoneanu, Anca Burlui, Alexandra Maria Macovei, Luana Andreea Bratoiu, Ioana Richter, Patricia Rezus, Elena Biomedicines Review Systemic sclerosis (SS) is a chronic autoimmune disorder, which has both cutaneous and systemic clinical manifestations. The disease pathogenesis includes a triad of manifestations, such as vasculopathy, autoimmunity, and fibrosis. Interleukin-6 (IL-6) has a special role in SS development, both in vascular damage and in the development of fibrosis. In the early stages, IL-6 participates in vascular endothelial activation and apoptosis, leading to the release of damage-associated molecular patterns (DAMPs), which maintain inflammation and autoimmunity. Moreover, IL-6 plays an important role in the development of fibrotic changes by mediating the transformation of fibroblasts into myofibroblasts. All of these are associated with disabling clinical manifestations, such as skin thickening, pulmonary fibrosis, pulmonary arterial hypertension (PAH), heart failure, and dysphagia. Tocilizumab is a humanized monoclonal antibody that inhibits IL-6 by binding to the specific receptor, thus preventing its proinflammatory and fibrotic actions. Anti-IL-6 therapy with Tocilizumab is a new hope for SS patients, with data from clinical trials supporting the favorable effect, especially on skin and lung damage. MDPI 2022-01-29 /pmc/articles/PMC8869570/ /pubmed/35203527 http://dx.doi.org/10.3390/biomedicines10020318 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Cardoneanu, Anca
Burlui, Alexandra Maria
Macovei, Luana Andreea
Bratoiu, Ioana
Richter, Patricia
Rezus, Elena
Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
title Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
title_full Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
title_fullStr Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
title_full_unstemmed Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
title_short Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?
title_sort targeting systemic sclerosis from pathogenic mechanisms to clinical manifestations: why il-6?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869570/
https://www.ncbi.nlm.nih.gov/pubmed/35203527
http://dx.doi.org/10.3390/biomedicines10020318
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