The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women

Abstract We aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were de...

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Autores principales:	Georgi Vasilev, Irena Manolova, Mariana Ivanova, Iskren Stanilov, Lyuba Miteva, Spaska Stanilova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ddcb275ef90f4c3da84e7d14860bbca7
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spelling	oai:doaj.org-article:ddcb275ef90f4c3da84e7d14860bbca72021-12-02T16:24:22ZThe role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women10.1038/s41598-021-94841-x2045-2322https://doaj.org/article/ddcb275ef90f4c3da84e7d14860bbca72021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94841-xhttps://doaj.org/toc/2045-2322Abstract We aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were determined by ELISA assays. A supervised dimensionality reducing approach (PLS-DA Analysis) was applied. All of the cytokines assayed were significantly elevated in the sera of RA female patients than healthy controls with fold change: 21-fold for IL-6; 6.1-fold for IL-17A; 2.5-fold for IL-23; 2.3-fold for IL-18; 1.94-fold for TNF-α; 1.7-fold for IL-12p40. According to the results of the PLS-DA analysis, IL-17A, IL-18, and TNF-α were of higher importance rank compared to IL-23 and IL-12p40. Women in the early stage of RA displayed significantly elevated IL-17A levels than those with longer disease duration: 8.04 pg/ml [8.04–175.3] vs 4.64 pg/ml [2.95–13.31], p = 0.007. IL-6 serum levels were related to higher disease activity. We have demonstrated altered cytokine production within female RA patients on different treatment regimens. Those on Tocilizumab therapy showed elevated IL-6 levels and decreased IL-17A versus the rest of the patients’ subgroups. In conclusion, our data support the pivotal role of IL-18 in addition to IL-6, IL-17A, and TNF-α as the hierarchical cytokines in the pathogenesis of RA, particularly valid for women. Therapy with biological agents targeting IL-18 in addition to the Th17 axis may be an adequate approach in RA patients.Georgi VasilevIrena ManolovaMariana IvanovaIskren StanilovLyuba MitevaSpaska StanilovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Georgi Vasilev Irena Manolova Mariana Ivanova Iskren Stanilov Lyuba Miteva Spaska Stanilova The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women
description	Abstract We aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were determined by ELISA assays. A supervised dimensionality reducing approach (PLS-DA Analysis) was applied. All of the cytokines assayed were significantly elevated in the sera of RA female patients than healthy controls with fold change: 21-fold for IL-6; 6.1-fold for IL-17A; 2.5-fold for IL-23; 2.3-fold for IL-18; 1.94-fold for TNF-α; 1.7-fold for IL-12p40. According to the results of the PLS-DA analysis, IL-17A, IL-18, and TNF-α were of higher importance rank compared to IL-23 and IL-12p40. Women in the early stage of RA displayed significantly elevated IL-17A levels than those with longer disease duration: 8.04 pg/ml [8.04–175.3] vs 4.64 pg/ml [2.95–13.31], p = 0.007. IL-6 serum levels were related to higher disease activity. We have demonstrated altered cytokine production within female RA patients on different treatment regimens. Those on Tocilizumab therapy showed elevated IL-6 levels and decreased IL-17A versus the rest of the patients’ subgroups. In conclusion, our data support the pivotal role of IL-18 in addition to IL-6, IL-17A, and TNF-α as the hierarchical cytokines in the pathogenesis of RA, particularly valid for women. Therapy with biological agents targeting IL-18 in addition to the Th17 axis may be an adequate approach in RA patients.
format	article
author	Georgi Vasilev Irena Manolova Mariana Ivanova Iskren Stanilov Lyuba Miteva Spaska Stanilova
author_facet	Georgi Vasilev Irena Manolova Mariana Ivanova Iskren Stanilov Lyuba Miteva Spaska Stanilova
author_sort	Georgi Vasilev
title	The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women
title_short	The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women
title_full	The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women
title_fullStr	The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women
title_full_unstemmed	The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women
title_sort	role of il-18 in addition to th17 cytokines in rheumatoid arthritis development and treatment in women
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ddcb275ef90f4c3da84e7d14860bbca7
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The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women

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