interleukin-8 and Polymyalgia-Rheumatica

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.. 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.. 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.. 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.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Chemokine CCL2; Cytokines; Female; Glucocorticoids; Humans; Interleukin-1alpha; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Muscle, Skeletal; Polymyalgia Rheumatica; Prednisolone; Tumor Necrosis Factor-alpha

This study was conducted to evaluate phagocyte function in patients with age-related chronic inflammatory conditions. It included 95 patients with PMR, 17 with GCA, 40 with EORA, and 25 age-matched HCs. Serum IL-8 was determined with a bead array. The chemotactic capacity, phagocytic ability, and oxidative burst activity of circulating leukocytes were determined with flow cytometry kits. Patients with active chronic inflammatory diseases showed a significant increase in circulating levels of IL-8 that remained elevated in patients with PMR or EORA, despite treatment. No correlation was found between circulating IL-8 and the migratory capacity of neutrophils. Neutrophils from patients with active EORA without stimulus and after fMLP stimuli showed a higher capacity to migrate than those of the HCs (P=0.033). The phagocytic activity of granulocytes in the patients with GCA was significantly higher than in the HCs and the patients with PMR or EORA (P<0.05). The percentage and MFI of phagocytes that produce ROIs when stimulated with Escherichia coli was significantly reduced in neutrophils and monocytes from the patients with age-restricted inflammatory conditions. We concluded that the effector functions of phagocytes, determined to be chemotaxis, phagocytosis, and oxidative burst, are deregulated in age-restricted inflammatory disorders and may have a pathogenic role.

Topics: Acute-Phase Reaction; Age Factors; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Chemotaxis, Leukocyte; Chronic Disease; Female; Giant Cell Arteritis; Humans; Interleukin-8; Male; Middle Aged; Neutrophils; Phagocytes; Polymyalgia Rheumatica; Respiratory Burst

To evaluate the insulin sensitivity (IS) and levels of peptides with impact on IS in polymyalgia rheumatica (PMR) before and after prednisolone treatment.. Fifteen PMR patients and 15 controls were included. Subjects were studied before and after treatment with prednisolone for 14 days (20 mg/day). Composite IS indices were calculated from glucose and insulin concentrations during an oral glucose tolerance test (OGTT). Plasma concentrations of tumour necrosis factor alpha (TNF), interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), resistin, leptin, and adiponectin were measured.. Prednisolone abolished symptoms and increased physical activity within 1–2 days; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normalized at day 14. Before treatment, IS was lower in patients vs. controls (p < 0.001). Following treatment, IS was restored in patients (p < 0.01) but not changed in controls (p > 0.05). IL-6, TNF, and IL-8 were higher in patients vs. controls before treatment (p < 0.05–0.001), and decreased after treatment in patients (p < 0.001) but did not change in controls. Before treatment, adiponectin was lower in patients vs. controls (p < 0.05). During treatment, adiponectin increased in both groups (p < 0.05). Leptin did not differ between untreated patients and controls but increased in both groups (p < 0.05). MCP-1 and resistin did not differ (p > 0.05).. IS is decreased in PMR, probably reflecting abnormal cytokine and adipokine levels. Treatment with prednisolone improves IS along with normalization of cytokine and adipokine levels and physical activity.

Topics: Adiponectin; Aged; Aged, 80 and over; Blood Glucose; Case-Control Studies; Chemokine CCL2; Chemokines; Cytokines; Female; Glucocorticoids; Humans; Insulin; Insulin Resistance; Interleukin-6; Interleukin-8; Leptin; Male; Middle Aged; Motor Activity; Polymyalgia Rheumatica; Prednisolone; Resistin; Tumor Necrosis Factor-alpha