Increased Muscle Interstitial Levels of Inflammatory Cytokines in Polymyalgia Rheumatica

Arthritis Rheum. 2010 Dec;62(12):3768-75. doi: 10.1002/art.27728.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • C-Reactive Protein / metabolism
  • Chemokine CCL2 / metabolism
  • Cytokines / metabolism*
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism*
  • Polymyalgia Rheumatica / drug therapy*
  • Polymyalgia Rheumatica / metabolism*
  • Prednisolone / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Cytokines
  • Glucocorticoids
  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Prednisolone