Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly-onset rheumatoid arthritis

Cutolo, Maurizio; Montecucco, Carlomaurizio; Cavagna, Lorenzo; Caporali, Roberto; Capellino, Silvia; Montagna, Paola; Fazzuoli, Laura; Villaggio, Barbara; Seriolo, Bruno; Sulli, Alberto

doi:10.1136/ard.2006.051979

Cited by 71 publications

(69 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In PMR patients, elevated blood levels of IL-6, which were markedly decreased following glucocorticoid treatment, were found not only in our study, but also in several other studies (26)(27)(28)(29). Interestingly, it has been reported that plasma IL-6 levels rapidly return to increased levels following brief withdrawal of prednisolone treatment (27), suggesting that the underlying cause of the high IL-6 production in PMR is not eliminated in parallel with clinical remission induced by prednisolone.…”

Section: Discussionsupporting

confidence: 61%

“…The importance of IL-1␣/␤, IL-1Ra, IL-8, MCP-1, and TNF␣ in PMR is a subject of controversy, with differing reports on the blood levels of these cytokines and chemokines (26,28,29,(31)(32)(33). Interestingly, IL-1 receptors have been found to be overexpressed in the muscle nuclei and sarcolemma of patients with polymyositis and dermatomyositis, and it is possible that IL-1 impairs muscle fiber function by mechanisms other than muscle fiber damage (34).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Kreiner¹,

Langberg²,

Galbo³

2010

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Polymyalgia rheumatica (PMR) is characterized by aching of the proximal muscles and increased blood levels of markers of inflammation. Despite the muscle complaints, the current view is that symptoms are caused by inflammation in synovial structures. The purpose of this study was to elucidate the disease mechanisms in symptomatic muscles by measuring interstitial levels of cytokines before and after prednisolone treatment.Methods. Twenty glucocorticoid-naive patients newly diagnosed as having PMR and 20 control subjects were studied before and after 14 days of prednisolone therapy (20 mg/day). Interstitial concentrations of interleukin-1␣/␤ (IL-1␣/␤), IL-1 receptor antagonist, IL-6, IL-8, tumor necrosis factor ␣ (TNF␣), and monocyte chemoattractant protein 1 were measured in symptomatic vastus lateralis and trapezius muscles using the microdialysis technique. Plasma levels were measured simultaneously.Results. Prednisolone abolished symptoms in all of the PMR patients within 1-2 days; the erythrocyte sedimentation rate and C-reactive protein levels were normalized on day 14. In both muscles, interstitial concentrations of all cytokines were markedly higher (P < 0.05) in the PMR patients than in the controls before treatment. In both patients and controls, interstitial levels of most cytokines were higher than plasma levels, with the exception of IL-1␣ and TNF␣, which were lower in both groups. In the PMR patients, interstitial concentrations were normalized after prednisolone treatment.Conclusion. This study introduces a novel view of PMR, indicating that increased interstitial levels of inflammatory cytokines in symptomatic muscles play a role in the pathophysiology of the disease and that cytokines may be released locally. To explore the disease specificity, similar studies in other primary inflammatory conditions are warranted.

show abstract

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Kreiner¹,

Langberg²,

Galbo³

2010

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Our data revealing age-related reduction of DNA methylation of the TNF promoter suggest that age-related loss of the epigenetic signature of this cytokine may contribute to inflammaging and contributing to the pathogenesis of late onset rheumatic diseases such as PMR and RA in which this cytokine has been shown to a pivotal mediator of chronic inflammation [24,25].…”

Section: Discussionmentioning

confidence: 80%

Age-related loss of CpG methylation in the tumour necrosis factor promoter

et al. 2011

View full text Add to dashboard Cite

Background: Dysregulated production of TNF has been implicated in the pathogenesis and severity of inflammatory rheumatic diseases, many of which show age-related increased incidence. Ageing is also associated with changes in the immune system including higher systemic levels of pro-inflammatory cytokines.Methylation of DNA is an important regulator of gene expression and changes with age.Objective: In this study we investigated whether the DNA methylation status of the TNF promoter changed with age in peripheral blood leukocytes and macrophages. Methods and results:Using pyrosequencing assays we detected age-related demethylation of CpG motifs (-304, -245 and -239) Conclusions: These data suggest a potential role of accrued changes in DNA methylation in the development of age-related inflammatory diseases, such as rheumatoid arthritis and polymyalgia rheumatica, in which TNF is a pivotal mediator.3

show abstract

“…Increased serum concentrations of proinflammatory cytokines, including IL-1ß, TNF-α, and IL-6, in patients with PMR have been reported, but no elevation of IL-1ß or TNF-α was found in other reports 1,2 . Only IL-6 has been observed to be consistently high in patients with active disease [4][5][6] . IL-6 is recognized as the most sensitive indicator of disease activity and course and therefore IL-6 inhibition with tocilizumab may constitute a novel strategy for treatment of PMR.…”

Section: To the Editormentioning

confidence: 99%

Tocilizumab Ameliorates Clinical Symptoms in Polymyalgia Rheumatica: Figure 1.

Hagihara¹,

Kawase²,

Tanaka³

et al. 2010

J Rheumatol

View full text Add to dashboard Cite

Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly-onset rheumatoid arthritis

Abstract: Different cytokine and steroidal hormone patterns suggest that patients with PMR and those with EORA/PMR seem to be have a more intensive inflammatory reaction and are more efficient responders to glucocorticoid treatment than patients with EORA.

Cited by 71 publications

References 32 publications

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Age-related loss of CpG methylation in the tumour necrosis factor promoter

Tocilizumab Ameliorates Clinical Symptoms in Polymyalgia Rheumatica: Figure 1.

Contact Info

Product

Resources

About