Mechanism of exacerbation of rheumatoid synovitis by total-dose iron-dextran infusion: in-vivo demonstration of iron-promoted oxidant stress.

The mechanism by which a synovial flare occurred in a patient with rheumatoid arthritis after intravenous infusion of iron-dextran was investigated. After the infusion, serum and synovial-fluid iron-binding capacity became saturated, giving rise to low-molecular-mass iron chelates with the capacity to cause oxidative damage ("bleomycin-iron"). At the same time lipid peroxidation and the concentration of oxidised ascorbic acid (dehydroascorbate) increased in both serum and synovial fluid, and red-cell glutathione fell. These changes corresponded closely to an exacerbation of rheumatoid synovitis. Hepatic function was transiently disturbed 7 days after the infusion, reflecting hepatic oxidant stress within the iron-loaded liver. Such changes provide clear evidence that iron-catalysed oxidative reactions influence the inflammatory process in human beings.