Iron, lactoferrin and iron regulatory protein activity in the synovium; relative importance of iron loading and the inflammatory response

Abstract

Objectives - To determine the ability of lactoferrin in rheumatoid arthritis (RA) synovial fluid to bind 'free' iron, and to study the regulatory mechanisms therein that control iron homeostasis. Methods - 'Free' iron was determined by the bleomycin assay and lactoferrin concentrations by enzyme linked immunosorbent assay. The activities of iron regulatory protein (IRP) and NF-κB in synovial fluid cells were assayed by mobility shift assay. Results - 30% of synovial fluids contained 'free' iron and in these, lactoferrin concentrations were significantly lower than in those with no 'free' iron (p<0.01). Addition of exogenous lactoferrin consistently reduced the amount of 'free' iron in positive synovial fluids. IRP activity in synovial cells did not correlate with synovial fluid iron concentrations but did correlate with NF-κB activation and with serum C reactive protein. Conclusion - Lactoferrin may prevent iron mediated tissue damage in RA by reducing 'free' synovial iron concentration when inflammatory stimuli have disregulated IRP mediated iron homeostasis.