Circadian variation in plasma IL-6 and the role of modified-release prednisone in polymyalgia rheumatica

Zakout, Samy; Clarke, Lynsey; Jessop, David S.; Straub, Rainer H.; Kirwan, John R.

doi:10.2217/ijr.14.29

Cited by 3 publications

(5 citation statements)

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“…This is in accord with and adds to previous findings obtained in the morning [ 9 , 13 , 14 ]. Our findings also confirm the previous observation that, in PMR, prednisolone treatment diminishes IL-6 peak concentration and 24-h AUC [ 26 ]. In the patients with PMR in the present study, prednisolone diminished melatonin concentrations as well (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…Previously, diurnal variation was indicated in a study of nocturnal cytokine levels in healthy men, the study reporting that IL-1β and IL-6 were more likely to be above detection limits during sleep than during preceding wakefulness [ 25 ]. Furthermore, in a study of patients with PMR with no control subjects, IL-6 showed a diurnal variation comparable to the present findings [ 26 ]. In contrast, various other cytokines showed no clear indication of circadian variation [ 26 ].…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, in a study of patients with PMR with no control subjects, IL-6 showed a diurnal variation comparable to the present findings [ 26 ]. In contrast, various other cytokines showed no clear indication of circadian variation [ 26 ]. In RA, diurnal variation in cytokine concentrations, albeit less comprehensively than in the present study of PMR, has been reported and proposed to be partly responsible for the circadian rhythm of the clinical symptoms [ 1 , 5 , 20 ].…”

Section: Discussionsupporting

confidence: 90%

“…The present finding in PMR of a similar diurnal variation in cytokines and symptoms indicates that also in PMR adaptation of the timing of GC administration to the chronobiology of the disease would optimize the treatment. In fact, preliminary experiments have been reported to show positive outcomes of such an approach, with reductions in IL-6 levels and morning stiffness being more pronounced upon administration of prednisolone in the night than in the morning [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Circadian variations in clinical symptoms and concentrations of inflammatory cytokines, melatonin, and cortisol in polymyalgia rheumatica before and during prednisolone treatment: a controlled, observational, clinical experimental study

Galbo

Kall

2016

Arthritis Res Ther

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BackgroundIn contrast to rheumatoid arthritis (RA), no systematic investigation of diurnal variation has been carried out in polymyalgia rheumatica (PMR). The aim of the study was to provide the often-requested documentation of the 24-h time course of clinical symptoms in PMR and relate them to concentrations during the day of melatonin, inflammatory cytokines, and cortisol. Furthermore, the effects of 14 days of prednisolone treatment were studied.MethodsTen glucocorticoid-naive patients newly diagnosed with PMR and seven non-PMR control subjects were studied for 24 h before treatment and during the 14th day of treatment with 20 mg/day of prednisolone. Global pain and generalized muscle stiffness were monitored by using visual analogue scales, and blood was drawn repeatedly.ResultsIn untreated patients, pain and stiffness peaked in the early morning, showing a plateau between 04:00 and 08:00, and then declined to a nadir at 16:00 (2P < 0.05). Plasma concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, IL-1β, and IL-4 varied with time in both groups (2P < 0.05) and peaked between 04:00 and 08:00. Furthermore, except for IL-1β, concentrations of these cytokines and of IL-10 were higher throughout the 24-h observation period in patients than in control subjects (2P < 0.05). Also, melatonin and cortisol were consistently higher in patients (2P < 0.05) and varied with time (2P < 0.05), peaking around 02:00 and 08:00, respectively. In patients, prednisolone abolished symptoms, normalized C-reactive protein, and reduced melatonin, IL-6, IL-8, and TNF-α concentrations (2P < 0.05), while IL-10 increased between 10:00 and 14:00.ConclusionsIn PMR, key symptoms show diurnal variation. Furthermore, in PMR, concentrations of melatonin, several pro- and anti-inflammatory cytokines, and cortisol are increased throughout the day and show diurnal variation, as also seen in healthy subjects. The time courses and the inhibitory effects of prednisolone indicate that in PMR, as proposed for RA, melatonin stimulates cytokine production, which in turn accounts at least partly for the symptoms. Furthermore, overall, cortisol may downregulate cytokine production and symptoms. Stimulation of IL-10 secretion may participate in the anti-inflammatory effects of prednisolone. These findings support use of chronotherapy in PMR and encourage study of circadian variations in other inflammatory autoimmune diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1072-4) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Circadian variations in clinical symptoms and concentrations of inflammatory cytokines, melatonin, and cortisol in polymyalgia rheumatica before and during prednisolone treatment: a controlled, observational, clinical experimental study

Galbo

Kall

2016

Arthritis Res Ther

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show abstract

“…These findings mirror two previous studies in polymyalgia rheumatica (PMR). One showed a clear trend for improved short-term outcomes using DR-prednisone as compared to IR-prednisone [11], and another showed that 7 mg of DR-prednisone given in the evening achieved a similar percentage reduction in mean duration of morning stiffness as achieved with twice the dose of prednisolone in the morning [12].…”

Section: Discussionmentioning

confidence: 98%