Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines

<b>Background:</b> Chronic venous disease (CVD) comprises a set of vascular disorders that affect the venous system with important local and systemic repercussions. A growing body of evidence displays the relationship between suffering from CVD and a marked deregulation of the immune inf...

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Main Authors: Oscar Fraile-Martinez, Cielo García-Montero, Ana María Gomez-Lahoz, Felipe Sainz, Julia Bujan, Silvestra Barrena-Blázquez, Laura López-González, Raul Díaz-Pedrero, Melchor Álvarez-Mon, Natalio García-Honduvilla, Miguel A. Saez, Jorge Monserrat, Miguel A. Ortega
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Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/150
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author Oscar Fraile-Martinez
Cielo García-Montero
Ana María Gomez-Lahoz
Felipe Sainz
Julia Bujan
Silvestra Barrena-Blázquez
Laura López-González
Raul Díaz-Pedrero
Melchor Álvarez-Mon
Natalio García-Honduvilla
Miguel A. Saez
Jorge Monserrat
Miguel A. Ortega
author_facet Oscar Fraile-Martinez
Cielo García-Montero
Ana María Gomez-Lahoz
Felipe Sainz
Julia Bujan
Silvestra Barrena-Blázquez
Laura López-González
Raul Díaz-Pedrero
Melchor Álvarez-Mon
Natalio García-Honduvilla
Miguel A. Saez
Jorge Monserrat
Miguel A. Ortega
author_sort Oscar Fraile-Martinez
collection DOAJ
description <b>Background:</b> Chronic venous disease (CVD) comprises a set of vascular disorders that affect the venous system with important local and systemic repercussions. A growing body of evidence displays the relationship between suffering from CVD and a marked deregulation of the immune inflammatory system. In this sense, the previous literature has reported some significant changes in the level of various circulating inflammatory parameters in these patients. However, more research is required to detail and deepen this complex relationship. <b>Methods:</b> In this work, we studied, using a multiplex technique, the levels of circulating cytokines and chemokines detectable in the serum of 40 patients with CVD and compared it with 38 healthy controls (HCs). In parallel, we performed Spearman’s correlation analysis to explore potential inflammatory networks in CVD. <b>Results:</b> In this study, we measured circulating cytokines and chemokines in CVD patients using a multiplex assay. Results showed increased levels of several pro-inflammatory mediators (IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-12, IL-17A, IL-23, TNF-α, IFN-γ, fractalkine, ITAC, and GM-CSF) and a decrease in IL-13, with no significant changes in IL-4, IL-10, IL-21, MIP-1α, MIP-1β, or MIP-3α. The Spearman correlation analysis revealed strong, positive correlations among several inflammatory mediators in HC, particularly between TNF-alpha, IL-1β, IL-17A, and IL-23, forming a highly interconnected cytokine network. In contrast, CVD patients showed fewer, weaker, and distinct correlations, with new associations such as IFN-γ with IL-1β and IL-23, suggesting a disrupted inflammatory profile. <b>Conclusions:</b> The distinct inflammatory profile in CVD patients, characterized by altered cytokine and chemokine levels and a less coordinated cytokine network, underscores the reconfiguration of inflammatory pathways in this condition. These findings highlight potential therapeutic targets aimed at restoring immune balance and mitigating chronic inflammation in CVD.
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spelling doaj-art-6b2a7d7d346a4060b500de38c317d5fe2025-01-24T13:24:11ZengMDPI AGBiomedicines2227-90592025-01-0113115010.3390/biomedicines13010150Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and ChemokinesOscar Fraile-Martinez0Cielo García-Montero1Ana María Gomez-Lahoz2Felipe Sainz3Julia Bujan4Silvestra Barrena-Blázquez5Laura López-González6Raul Díaz-Pedrero7Melchor Álvarez-Mon8Natalio García-Honduvilla9Miguel A. Saez10Jorge Monserrat11Miguel A. Ortega12Department of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainRamón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, SpainRamón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, SpainRamón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, SpainDepartment of Medicine and Medical Specialities (CIBEREHD), Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain<b>Background:</b> Chronic venous disease (CVD) comprises a set of vascular disorders that affect the venous system with important local and systemic repercussions. A growing body of evidence displays the relationship between suffering from CVD and a marked deregulation of the immune inflammatory system. In this sense, the previous literature has reported some significant changes in the level of various circulating inflammatory parameters in these patients. However, more research is required to detail and deepen this complex relationship. <b>Methods:</b> In this work, we studied, using a multiplex technique, the levels of circulating cytokines and chemokines detectable in the serum of 40 patients with CVD and compared it with 38 healthy controls (HCs). In parallel, we performed Spearman’s correlation analysis to explore potential inflammatory networks in CVD. <b>Results:</b> In this study, we measured circulating cytokines and chemokines in CVD patients using a multiplex assay. Results showed increased levels of several pro-inflammatory mediators (IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-12, IL-17A, IL-23, TNF-α, IFN-γ, fractalkine, ITAC, and GM-CSF) and a decrease in IL-13, with no significant changes in IL-4, IL-10, IL-21, MIP-1α, MIP-1β, or MIP-3α. The Spearman correlation analysis revealed strong, positive correlations among several inflammatory mediators in HC, particularly between TNF-alpha, IL-1β, IL-17A, and IL-23, forming a highly interconnected cytokine network. In contrast, CVD patients showed fewer, weaker, and distinct correlations, with new associations such as IFN-γ with IL-1β and IL-23, suggesting a disrupted inflammatory profile. <b>Conclusions:</b> The distinct inflammatory profile in CVD patients, characterized by altered cytokine and chemokine levels and a less coordinated cytokine network, underscores the reconfiguration of inflammatory pathways in this condition. These findings highlight potential therapeutic targets aimed at restoring immune balance and mitigating chronic inflammation in CVD.https://www.mdpi.com/2227-9059/13/1/150chronic venous disease (CVD)circulating cytokines/chemokinesmultiplex
spellingShingle Oscar Fraile-Martinez
Cielo García-Montero
Ana María Gomez-Lahoz
Felipe Sainz
Julia Bujan
Silvestra Barrena-Blázquez
Laura López-González
Raul Díaz-Pedrero
Melchor Álvarez-Mon
Natalio García-Honduvilla
Miguel A. Saez
Jorge Monserrat
Miguel A. Ortega
Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines
Biomedicines
chronic venous disease (CVD)
circulating cytokines/chemokines
multiplex
title Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines
title_full Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines
title_fullStr Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines
title_full_unstemmed Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines
title_short Evidence of Inflammatory Network Disruption in Chronic Venous Disease: An Analysis of Circulating Cytokines and Chemokines
title_sort evidence of inflammatory network disruption in chronic venous disease an analysis of circulating cytokines and chemokines
topic chronic venous disease (CVD)
circulating cytokines/chemokines
multiplex
url https://www.mdpi.com/2227-9059/13/1/150
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