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The Contribution of Muscle Innate Immunity to Uremic Cachexia

Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexi...

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Autores principales: Esposito, Pasquale, Verzola, Daniela, Saio, Michela, Picciotto, Daniela, Frascio, Marco, Laudon, Alessandro, Zanetti, Valentina, Brunori, Giuliano, Garibotto, Giacomo, Viazzi, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10343562/
https://www.ncbi.nlm.nih.gov/pubmed/37447158
http://dx.doi.org/10.3390/nu15132832
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author Esposito, Pasquale
Verzola, Daniela
Saio, Michela
Picciotto, Daniela
Frascio, Marco
Laudon, Alessandro
Zanetti, Valentina
Brunori, Giuliano
Garibotto, Giacomo
Viazzi, Francesca
author_facet Esposito, Pasquale
Verzola, Daniela
Saio, Michela
Picciotto, Daniela
Frascio, Marco
Laudon, Alessandro
Zanetti, Valentina
Brunori, Giuliano
Garibotto, Giacomo
Viazzi, Francesca
author_sort Esposito, Pasquale
collection PubMed
description Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, “sterile” muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering “sterile” tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.
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spelling pubmed-103435622023-07-14 The Contribution of Muscle Innate Immunity to Uremic Cachexia Esposito, Pasquale Verzola, Daniela Saio, Michela Picciotto, Daniela Frascio, Marco Laudon, Alessandro Zanetti, Valentina Brunori, Giuliano Garibotto, Giacomo Viazzi, Francesca Nutrients Review Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, “sterile” muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering “sterile” tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW. MDPI 2023-06-21 /pmc/articles/PMC10343562/ /pubmed/37447158 http://dx.doi.org/10.3390/nu15132832 Text en © 2023 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
Esposito, Pasquale
Verzola, Daniela
Saio, Michela
Picciotto, Daniela
Frascio, Marco
Laudon, Alessandro
Zanetti, Valentina
Brunori, Giuliano
Garibotto, Giacomo
Viazzi, Francesca
The Contribution of Muscle Innate Immunity to Uremic Cachexia
title The Contribution of Muscle Innate Immunity to Uremic Cachexia
title_full The Contribution of Muscle Innate Immunity to Uremic Cachexia
title_fullStr The Contribution of Muscle Innate Immunity to Uremic Cachexia
title_full_unstemmed The Contribution of Muscle Innate Immunity to Uremic Cachexia
title_short The Contribution of Muscle Innate Immunity to Uremic Cachexia
title_sort contribution of muscle innate immunity to uremic cachexia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10343562/
https://www.ncbi.nlm.nih.gov/pubmed/37447158
http://dx.doi.org/10.3390/nu15132832
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