Ameliorative effect of ozone on cytokine production in mice injected with human rheumatoid arthritis synovial fibroblast cells.
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.
Chang
Johnson D S
JD
Department of Orthopaedics, Johnson General Hospital, 425 Chang Tsau Road, Changhua, Taiwan ROC. jonhsonchangmd@yahoo.com.tw
Lu
Hou-Shan
HS
Chang
Ye-Fun
YF
Wang
David
D
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000494:pharmacology*; D010126:Ozone / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013264:Stifle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D010083:Oxidants, Photochemical; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone