The adrenal steroid status in relation to inflammatory cytokines (interleukin‐6 and tumour necrosis factor) in polymyalgia rheumatica

Straub, Rainer H.; Glück, Thomas; Cutolo, Maurizio; Georgi, J.; Helmke, K.; Schölmerich, Jürgen; Vaith, P; Läng, B

doi:10.1093/rheumatology/39.6.624

Cited by 73 publications

(54 citation statements)

References 37 publications

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“…Although IL-6 is involved in the worsening of synovial inflammation of RA (6), only a few studies have evaluated IL-6 as a surrogate marker of joint inflammation and predictor of structural damage, with divergent results (1,7).…”

Section: Supported By the Espoir (Etude Et Suivi Des Polyarthritesmentioning

confidence: 99%

Evaluation of Serum Interleukin‐6 Level as a Surrogate Marker of Synovial Inflammation and as a Factor of Structural Progression in Early Rheumatoid Arthritis: Results From a French National Multicenter Cohort

Baillet¹,

Gossec

Paternotte

et al. 2015

Arthritis Care & Research

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Objective. Interleukin-6 (IL-6) is a key cytokine in rheumatoid arthritis pathogenesis. We aimed to analyze the association between IL-6 serum levels and joint inflammation at baseline and the correlation of time-integrated IL-6 values with structural damage during the first 36 months of early arthritis. Methods. IL-6 was assessed by 2 different methods in 813 patients of the French early arthritis cohort ESPOIR (Etude et Suivi des Polyarthrites Indiff erenci ees R ecentes) over 36 months. IL-6 and C-reactive protein (CRP) changes were correlated to radiographic progression assessed by the total Sharp/van der Heijde score (SHS). Synovium inflammation was assessed in a subgroup of 126 patients by ultrasonography (US). The relationship between SHS change and IL-6 or CRP levels at baseline was investigated by a univariate regression and a multivariable analysis. A longitudinal model nested by visit and patient was conducted to assess the role of IL-6 on SHS at each visit. Results. At baseline, IL-6 was more strongly correlated with the swollen joint count than CRP level. In the univariate analysis, the time-integrated value of IL-6 was more strongly correlated with the swollen joint count and the variation of SHS than timeintegrated CRP level. Baseline IL-6 was not independently associated with SHS change. Longitudinal models nested by patient showed that IL-6 levels were associated with structural damage independently from the Disease Activity Score in 28 joints, smoking status, rheumatoid factor, and anti-citrullinated protein peptide antibody serology, treatments, and CRP levels. Conclusion. IL-6 level was a marker of US synovitis at baseline. Repeated measurements of IL-6 are associated with structural damage.

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Section: Supported By the Espoir (Etude Et Suivi Des Polyarthritesmentioning

confidence: 99%

Evaluation of Serum Interleukin‐6 Level as a Surrogate Marker of Synovial Inflammation and as a Factor of Structural Progression in Early Rheumatoid Arthritis: Results From a French National Multicenter Cohort

Baillet¹,

Gossec

Paternotte

et al. 2015

Arthritis Care & Research

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“…There are indications for circadian variation of TNF-α and IL-6 secretion with peak values in the early morning hours. Therefore, given the known high GC sensitivity of PMR, time-adapted GC therapy can be hypothesized to be likely more effective than the currently used standard regimen in improving clinical symptoms [27,28,29,30]. …”

Section: Mediators Of Circadian Clinical Symptoms In Arthritismentioning

confidence: 99%

Circadian Use of Glucocorticoids in Rheumatoid Arthritis

Cutolo

Sulli

Pincus

2014

Neuroimmunomodulation

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A clear temporal relationship exists in rheumatoid arthritis (RA) patients between increased nocturnal levels of pro-inflammatory cytokines, such as TNF-α and interleukin (IL)-6, pro-inflammatory hormones (i.e. melatonin, prolactin) and insufficient night production of the anti-inflammatory cortisol (circadian rhythm). Under long-standing chronic stress of disease, insufficient cortisol is available to inhibit an ongoing nocturnal immune/inflammatory reaction. Clinical RA symptoms follow the same circadian rhythm with highest morning severity. Chronotherapy with nighttime glucocorticoid (GC) availability optimizes the treatment of RA patients with low-dose GCs through more efficient targeting of mediators of the immune/inflammatory reaction during the night to be available on arising. Circadian use of low-dose, long-term prednisone, by using night-release formulations (ingested at 10 to 11 p.m.) especially in early RA patients, appears characterized by a significantly superior efficacy on decreasing morning stiffness and IL-6 serum levels, compared to conventional daytime immediate-release prednisone. Shift from medium-dose, immediate-release prednisone (over 7.5-10 mg/day) to night-release formulations GC low-dose, long-term chronotherapy requires a gradual passage, since the hypothalamic-pituitary-adrenal axis of the treated RA patients, potentially altered by a negative feedback induced by the medium/high daily exogenous GC administration, needs time to re-synchronize control of endogenous GC production into a circadian and more physiological nocturnal hormone availability/optimized efficacy.

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“…IL-6 is known to be an important cytokine in the pathogenesis of PMR. The IL-6 level in patients with active PMR has been found to be signifi cantly higher compared to healthy control groups in previous studies and it has been determined that the IL-6 level decreases with GC treatment [7][8][9][10][11][12][13][14]. The IL-6 level of patients during a relapse has also been determined to be signifi cantly higher than that of patients in remission [15].…”

Section: Discussionmentioning

confidence: 99%

Remission of Glucocorticoid-Resistant Polymyalgia Rheumatica achieved with Tocilizumab: 2 Case Reports

Enginar¹

2017

Rheumatica Acta: Open Access

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The adrenal steroid status in relation to inflammatory cytokines (interleukin‐6 and tumour necrosis factor) in polymyalgia rheumatica

Cited by 73 publications

References 37 publications

Evaluation of Serum Interleukin‐6 Level as a Surrogate Marker of Synovial Inflammation and as a Factor of Structural Progression in Early Rheumatoid Arthritis: Results From a French National Multicenter Cohort

Evaluation of Serum Interleukin‐6 Level as a Surrogate Marker of Synovial Inflammation and as a Factor of Structural Progression in Early Rheumatoid Arthritis: Results From a French National Multicenter Cohort

Circadian Use of Glucocorticoids in Rheumatoid Arthritis

Remission of Glucocorticoid-Resistant Polymyalgia Rheumatica achieved with Tocilizumab: 2 Case Reports

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