High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis

IntroductionGlucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood.MethodsWe investigated long-tr...

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Main Authors: Anna Petrackova, Pavel Horak, Jakub Savara, Martina Skacelova, Eva Kriegova
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505615/full
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author Anna Petrackova
Pavel Horak
Jakub Savara
Jakub Savara
Martina Skacelova
Eva Kriegova
author_facet Anna Petrackova
Pavel Horak
Jakub Savara
Jakub Savara
Martina Skacelova
Eva Kriegova
author_sort Anna Petrackova
collection DOAJ
description IntroductionGlucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood.MethodsWe investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23).Results and discussionPatients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil–lymphocyte and platelet–lymphocyte ratios and a decreased lymphocyte–monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.
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spelling doaj-art-63b3553cd43e486aa8063ad3129e849b2025-08-20T01:57:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15056151505615High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritisAnna Petrackova0Pavel Horak1Jakub Savara2Jakub Savara3Martina Skacelova4Eva Kriegova5Department of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, CzechiaDepartment of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, CzechiaDepartment of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, CzechiaDepartment of Computer Science, Faculty of Electrical Engineering and Computer Science, Technical University of Ostrava, Ostrava, CzechiaDepartment of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, CzechiaDepartment of Immunology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, CzechiaIntroductionGlucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood.MethodsWe investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23).Results and discussionPatients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil–lymphocyte and platelet–lymphocyte ratios and a decreased lymphocyte–monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505615/fullautoimmune diseasesadverse effects of glucocorticoidssystemic inflammationcytokine profilelong-treated patientsdisease activity
spellingShingle Anna Petrackova
Pavel Horak
Jakub Savara
Jakub Savara
Martina Skacelova
Eva Kriegova
High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis
Frontiers in Immunology
autoimmune diseases
adverse effects of glucocorticoids
systemic inflammation
cytokine profile
long-treated patients
disease activity
title High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis
title_full High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis
title_fullStr High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis
title_full_unstemmed High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis
title_short High cumulative glucocorticoid dose is associated with increased levels of inflammation-related mediators in active rheumatoid arthritis
title_sort high cumulative glucocorticoid dose is associated with increased levels of inflammation related mediators in active rheumatoid arthritis
topic autoimmune diseases
adverse effects of glucocorticoids
systemic inflammation
cytokine profile
long-treated patients
disease activity
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1505615/full
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