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Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with syste...

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Autores principales: Mercader-Salvans, Julia, García-González, María, Gómez-Bernal, Fuensanta, Quevedo-Abeledo, Juan C., de Vera-González, Antonia, González-Delgado, Alejandra, López-Mejías, Raquel, Martín-González, Candelaria, González-Gay, Miguel Á., Ferraz-Amaro, Iván
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531425/
https://www.ncbi.nlm.nih.gov/pubmed/37762312
http://dx.doi.org/10.3390/ijms241814006
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author Mercader-Salvans, Julia
García-González, María
Gómez-Bernal, Fuensanta
Quevedo-Abeledo, Juan C.
de Vera-González, Antonia
González-Delgado, Alejandra
López-Mejías, Raquel
Martín-González, Candelaria
González-Gay, Miguel Á.
Ferraz-Amaro, Iván
author_facet Mercader-Salvans, Julia
García-González, María
Gómez-Bernal, Fuensanta
Quevedo-Abeledo, Juan C.
de Vera-González, Antonia
González-Delgado, Alejandra
López-Mejías, Raquel
Martín-González, Candelaria
González-Gay, Miguel Á.
Ferraz-Amaro, Iván
author_sort Mercader-Salvans, Julia
collection PubMed
description Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01–0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16–0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3–0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. −0.04 [95%CI −0.08–(−0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. −0.02 [95%CI −0.04–(−0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02–0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.
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spelling pubmed-105314252023-09-28 Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus Mercader-Salvans, Julia García-González, María Gómez-Bernal, Fuensanta Quevedo-Abeledo, Juan C. de Vera-González, Antonia González-Delgado, Alejandra López-Mejías, Raquel Martín-González, Candelaria González-Gay, Miguel Á. Ferraz-Amaro, Iván Int J Mol Sci Article Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01–0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16–0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3–0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. −0.04 [95%CI −0.08–(−0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. −0.02 [95%CI −0.04–(−0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02–0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE. MDPI 2023-09-12 /pmc/articles/PMC10531425/ /pubmed/37762312 http://dx.doi.org/10.3390/ijms241814006 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 Article
Mercader-Salvans, Julia
García-González, María
Gómez-Bernal, Fuensanta
Quevedo-Abeledo, Juan C.
de Vera-González, Antonia
González-Delgado, Alejandra
López-Mejías, Raquel
Martín-González, Candelaria
González-Gay, Miguel Á.
Ferraz-Amaro, Iván
Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus
title Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus
title_full Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus
title_fullStr Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus
title_full_unstemmed Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus
title_short Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus
title_sort relationship between disease characteristics and circulating interleukin 6 in a well-characterized cohort of patients with systemic lupus erythematosus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531425/
https://www.ncbi.nlm.nih.gov/pubmed/37762312
http://dx.doi.org/10.3390/ijms241814006
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