Giant cell arteritis and polymyalgia rheumatica: Role of cytokines in the pathogenesis and implications for treatment

Martínez‐Taboada, Víctor M.; Álvarez, Lourdes Sanz; Ruiz-Soto, María; Marin-Vidalled, Maria Jose; López‐Hoyos, Marcos

doi:10.1016/j.cyto.2008.09.004

Cited by 84 publications

(62 citation statements)

References 90 publications

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“…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%

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Kreiner¹,

Langberg²,

Galbo³

2010

Arthritis & Rheumatism

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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.

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Section: Discussionmentioning

confidence: 99%

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Kreiner¹,

Langberg²,

Galbo³

2010

Arthritis & Rheumatism

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“…The pathogenesis of GCA remains unclear but CD4 + T cell is the key cell involved and the key cytokines are IFN-c (essential for granuloma formation) and IL-6 (for systemic response) [86,87].…”

Section: Gaint Cell Arteritis and Takayasu Arteritismentioning

confidence: 99%

Anti‐interleukin‐6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases

2011

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Interleukin (IL)‐6 is a cytokine with multiple biological activities. It contributes to host defense against pathogens, whereas accelerated production of IL‐6 plays a significant pathological role in various diseases. Clinical trials have demonstrated the efficacy of tocilizumab, a humanized anti‐IL‐6 receptor antibody, for patients with rheumatoid arthritis, Castleman's disease or juvenile idiopathic arthritis, leading to approval of this innovative drug for the treatment of these diseases. Since IL‐6 has been demonstrated to play a significant role in the development of various other autoimmune and inflammatory diseases, tocilizumab can be expected to become a novel drug for such diseases as well.

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“…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] .…”

Section: To the Editormentioning

confidence: 87%

“…The disease is characterized by aching and morning stiffness in the shoulders, neck, and pelvic girdles. Although the pathogenesis of PMR remains unknown, overproduction of proinflammatory cytokines has been demonstrated to contribute to its development 1,2 . Corticosteroids constitute the preferred treatment for PMR and prednisolone 10-20 mg/day is usually adequate.…”

Section: To the Editormentioning

confidence: 99%

Tocilizumab Ameliorates Clinical Symptoms in Polymyalgia Rheumatica: Figure 1.

Hagihara¹,

Kawase²,

Tanaka³

et al. 2010

J Rheumatol

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Giant cell arteritis and polymyalgia rheumatica: Role of cytokines in the pathogenesis and implications for treatment

Cited by 84 publications

References 90 publications

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

Anti‐interleukin‐6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases

Tocilizumab Ameliorates Clinical Symptoms in Polymyalgia Rheumatica: Figure 1.

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