Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

TY - JOUR

T1 - Increased muscle interstitial levels of inflammatory cytokines in polymyalgia rheumatica

AU - Kreiner, Frederik

AU - Langberg, Henning

AU - Galbo, Henrik

N1 - Copyright © 2010 by the American College of Rheumatology.

PY - 2010/12

Y1 - 2010/12

N2 - 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-1α/β (IL-1α/β), IL-1 receptor antagonist, IL-6, IL-8, tumor necrosis factor α (TNFα), 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-1α and TNFα, 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.

AB - 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-1α/β (IL-1α/β), IL-1 receptor antagonist, IL-6, IL-8, tumor necrosis factor α (TNFα), 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-1α and TNFα, 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.

KW - Aged

KW - Aged, 80 and over

KW - C-Reactive Protein

KW - Chemokine CCL2

KW - Cytokines

KW - Female

KW - Glucocorticoids

KW - Humans

KW - Interleukin-1alpha

KW - Interleukin-1beta

KW - Interleukin-6

KW - Interleukin-8

KW - Male

KW - Middle Aged

KW - Muscle, Skeletal

KW - Polymyalgia Rheumatica

KW - Prednisolone

KW - Tumor Necrosis Factor-alpha

U2 - 10.1002/art.27728

DO - 10.1002/art.27728

M3 - Journal article

C2 - 20812339

SN - 0004-3591

VL - 62

SP - 3768

EP - 3775

JO - Arthritis & Rheumatism

JF - Arthritis & Rheumatism

IS - 12

ER -