High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment
| Autor: | Grazyna Luszczykiewicz, Jacek Pazdur, Maria Ziolkowska, Jacek Szechiński, Maria Rell-Bakalarska, Anna Filipowicz-Sosnowska, Jacek Kowalczewski, Mariola Kurowska, Piotr Wiland, Wojciech Dziewczopolski, Wlodzimierz Maslinski, A Radzikowska |
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| Rok vydání: | 2002 |
| Předmět: |
musculoskeletal diseases
Adult medicine.medical_specialty medicine.medical_treatment Immunology Arthritis Receptors Cytoplasmic and Nuclear Enzyme-Linked Immunosorbent Assay Peripheral blood mononuclear cell Receptors Tumor Necrosis Factor Proinflammatory cytokine Arthritis Rheumatoid Rheumatology Osteoprotegerin Internal medicine Synovial Fluid medicine Immunology and Allergy Humans Receptors Tumor Necrosis Factor Type II Pharmacology (medical) Aged Glycoproteins Autoimmune disease Aged 80 and over business.industry Age Factors Antibodies Monoclonal Middle Aged medicine.disease Infliximab Neoplasm Proteins Tumor Necrosis Factor Decoy Receptors Endocrinology Cytokine Methotrexate Rheumatoid arthritis Antirheumatic Agents Tumor necrosis factor alpha business |
| Zdroj: | Arthritis and rheumatism. 46(7) |
| ISSN: | 0004-3591 |
| Popis: | Objective To test the hypotheses that 1) proinflammatory cytokines affect osteoprotegerin (OPG) and soluble receptor activator of nuclear factor κB ligand (sRANKL) production and therefore the OPG and sRANKL levels differ in rheumatoid arthritis (RA) patients in comparison with healthy individuals; and 2) anti–tumor necrosis factor α (anti–TNFα) therapy influences OPG and sRANKL levels. Methods Sera were obtained from healthy individuals or RA patients receiving the combination of infliximab and methotrexate. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were isolated from RA patients. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissue obtained at total knee replacement in RA patients. Supernatants from cells stimulated with cytokines were collected after culture in vitro. Concentrations of OPG and sRANKL were determined by enzyme-linked immunosorbent assays. Results A strong positive correlation between OPG concentration and age was observed in healthy individuals but not in RA patients. The OPG and sRANKL levels were higher in RA patients than in healthy controls. Cultured FLS spontaneously secreted much higher amounts of OPG than PBMCs or SFMCs. Proinflammatory cytokines enhanced OPG production. Anti-TNFα treatment resulted in the normalization of serum OPG and sRANKL levels in RA patients without influencing the OPG:sRANKL ratio. Conclusion Although higher serum levels of OPG and sRANKL are present in RA patients than in healthy individuals, the ratio of OPG:sRANKL is similar. There is an age-dependent increase of OPG but not sRANKL levels in healthy subjects. Anti-TNFα treatment results in the normalization of elevated levels of OPG and sRANKL in RA patients. |
| Databáze: | OpenAIRE |
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