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01 April 2004

Proinflammatory cytokines increase iron uptake into human monocytes and synovial fibroblasts from patients with rheumatoid arthritis

Joan F. Telfer, Jeremy H. Brock

Med Sci Monit 2004; 10(4): BR91-95 :: ID: 11624

Abstract

Background:It has been hypothesized that iron is stored in the synovium of patients with rheumatoid arthritis which perpetuates inflammation by aiding the production of oxygen free radicals. Proinflammatory cytokines are produced by macrophages and lymphocytes present within synovium and by mononuclear cells of in synovial fluid from patients with rheumatoid arthritis. There are two known systems for iron uptake. The first involves binding of iron to transferrin and uptake via transferrin receptors. The second involves uptake by low molecular weight organic anions such as ascorbate and citrate (non-transferrin bound uptake).
Material/Methods: Proinflammatory cytokines (IL-1, Il-6, TNF? and interferon ?) were added to fibroblasts isolated from patients with rheumatoid arthritis and human monocytes in culture and their effect on [sup]59[/sup]Fe-transferrin and citrate uptake was determined.
Results: Proinflammatory cytokines increase transferrin and non-transferrin bound iron uptake into human monocytes and increase transferrin-bound iron uptake by synovial fibroblasts, but have no effect on non-transferrin bound uptake into fibroblasts.
Conclusions: Proinflammatory cytokines produced in human rheumatoid arthritis synovium and synovial fluid may contribute to the accumulation of iron that occurs in rheumatoid arthritis synovium which may lead to damage to synovial fibroblasts, macrophages and lymphocytes.

Keywords: Arthritis, Rheumatoid - metabolism, Cells, Cultured, Citrates - metabolism, Cytokines - pharmacology, Fibroblasts - drug effects, Fibroblasts - metabolism, Iron - metabolism, Monocytes - drug effects, Monocytes - metabolism, Synovial Membrane - drug effects, Synovial Membrane - metabolism, Transferrin - metabolism, Arthritis, Rheumatoid - metabolism, Cells, Cultured, Citrates - metabolism, Cytokines - pharmacology, Fibroblasts - metabolism, Iron - metabolism, Monocytes - metabolism, Synovial Membrane - metabolism, Transferrin - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750