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

A. Petrackova, P. Horak, J. Savara, M. Skacelova, E. Kriegova

. 2024 ; 15 (-) : 1505615. [pub] 20241218

Language English Country Switzerland

Document type Journal Article

INTRODUCTION: Glucocorticoids (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. METHODS: We 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 DISCUSSION: Patients 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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$a INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.
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$a Horak, Pavel $u Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital, Olomouc, Czechia
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