Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by invasion of hyperplastic synovial cells and progressive joint destruction. Ozone therapy has been proposed as an immunomodulator and cellular metabolic activator which shows long-term anti-inflammatory effects and serves to reduce further the proinflammatory factors. We purified RA synovial fibroblast cells (RA-SFc) from patients and avoided contaminating macrophages by flow cytometry, then treated them with ozone. Following the observable decreased production of proinflammatory factors TNF-alpha, IL-1beta, and IL-6 from RA-SFc, we infused the cultured RA-SFc into joints of severe combined immunodeficiency mice. The mRNA and protein levels of the RA-SFc exposed to 3% and 5% ozone were the same. As a result, 3% and 5% ozone applied externally ameliorated the inflammatory reaction of RA without toxicity or serious side effects. Therefore, ozone injected into the knees of RA patients could become a valuable treatment, and we confirm the interactive mechanism between ozone and RA-SFc.
MeSH terms
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Animals
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Arthritis, Rheumatoid / drug therapy
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Arthritis, Rheumatoid / metabolism*
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Arthritis, Rheumatoid / pathology
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Cell Survival / drug effects
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Cells, Cultured
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Cytokines / genetics
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Cytokines / metabolism*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Female
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Fibroblasts / drug effects*
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Flow Cytometry
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Humans
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Injections, Intra-Articular
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Interleukin-1 / genetics
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Interleukin-1 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Mice
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Mice, SCID
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Oxidants, Photochemical / administration & dosage
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Oxidants, Photochemical / pharmacology*
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Ozone / administration & dosage
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Ozone / pharmacology*
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Stifle / drug effects
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Stifle / metabolism
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Stifle / pathology
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Synovial Membrane / drug effects*
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Synovial Membrane / metabolism
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Synovial Membrane / pathology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Cytokines
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Interleukin-1
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Interleukin-6
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Oxidants, Photochemical
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Ozone