Abstract
Statins exert favorable effects on lipoprotein metabolism but may also possess anti-inflammatory effects. Here, we explored the effects of atorvastatin in a model of adjuvant-induced arthritis in rat. Oral treatment with atorvastatin (1-10 mg/kg) from days 10 to 15 after arthritis induction caused inhibition of the increase in paw volume. Maximal inhibition occurred at a dose of 10 mg/kg. At this dose, atorvastatin markedly ameliorated the histopathological findings of joints obtained from day 16 of arthritic animals. This was mirrored by an effective blockade of neutrophil influx, as assessed by the tissue myeloperoxidase levels. The concentrations of the cytokines interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha and the chemokines CCL5 and CCL2 were significantly decreased in arthritic rats treated with atorvastatin. In contrast, the levels of interleukin-10 were enhanced by the drug treatment. The drug also prevented the hypernociception observed in the inflamed joints. These data clearly illustrate the therapeutic potential of a statin-sensitive pathway in inflammatory arthritis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / pharmacology*
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Analgesics / therapeutic use
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Anti-Inflammatory Agents / therapeutic use
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Arthritis, Experimental / metabolism
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Arthritis, Experimental / pathology
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Arthritis, Experimental / prevention & control*
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Atorvastatin
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Chemokine CCL2 / biosynthesis
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Chemokine CCL5 / biosynthesis
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Chemokines, CC / biosynthesis
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Dose-Response Relationship, Drug
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Edema / complications
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Edema / prevention & control
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Female
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Heptanoic Acids / pharmacology*
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Heptanoic Acids / therapeutic use
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Hindlimb / drug effects
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Hindlimb / pathology
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
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Hyperalgesia / etiology
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Hyperalgesia / prevention & control
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Interleukin-1 / biosynthesis
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Interleukin-10 / biosynthesis
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Interleukin-6 / biosynthesis
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Leukocytes / pathology
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Neutrophils / pathology
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Peroxidase / metabolism
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Pyrroles / pharmacology*
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Pyrroles / therapeutic use
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Rats
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Tarsal Joints / drug effects
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Tarsal Joints / pathology
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Time Factors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Analgesics
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Anti-Inflammatory Agents
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Ccl2 protein, rat
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Chemokine CCL2
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Chemokine CCL5
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Chemokines, CC
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Heptanoic Acids
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Interleukin-1
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Interleukin-6
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Pyrroles
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Tumor Necrosis Factor-alpha
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Interleukin-10
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Atorvastatin
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Peroxidase