IRON, LACTOFERRIN AND IRON REGULATORY PROTEIN-ACTIVITY IN THE SYNOVIUM - RELATIVE IMPORTANCE OF IRON LOADING AND THE INFLAMMATORY RESPONSE

Objectives-To determine the ability of lactoferrin in rheumatoid arthr itis (RA) synovial fluid to bind ''free'' iron, and to study the regul atory mechanisms therein that control iron homeostasis. Methods-''Free '' iron was determined by the bleomycin assay and lactoferrin concentr ations by enzyme linked immunosorbent assay. The activities of iron re gulatory protein (IRP) and NF-kappa B in synovial fluid cells were ass ayed by mobility shift assay. Results-30% of synovial fluids contained ''free'' iron and in these, lactoferrin concentrations were significa ntly lower than in those with no ''free'' iron (p<0.01). Addition of e xogenous lactoferrin consistently reduced the amount of ''free'' iron in positive synovial fluids. IRP activity in synovial cells did not co rrelate with synovial fluid iron concentrations but did correlate with NF-kappa B activation and with serum C reactive protein. Conclusion-L actoferrin may prevent iron mediated tissue damage in RA by reducing ' 'free'' synovial iron concentration when inflammatory stimuli have dis regulated IRP mediated iron homeostasis.