Effect of iron complexes on adjuvant arthritis in rats.

When a total dose infusion of iron dextran is given to anaemic rheumatoid patients an exacerbation of inflammatory synovitis in previously affected joints is observed. The adjuvant arthritis model of inflammation in rats has been used to investigate the mechanism of iron promoted synovitis. Either iron dextran (5 mg injected intravenously) with a dextran C control, or iron sorbitol (7.5 mg injected intramuscularly) with a sorbitol citrate complex control was given at the onset of clinical joint inflammation. Iron dextran significantly increased joint inflammation (assessed by joint scoring) at days 12, 13, 14, and 16 after injection. Similarly, iron sorbitol produced a significant increase in the joint score at days 17, 18, 19, and 21. In addition, extensive osteoporosis was observed in the rats treated with iron sorbitol. These pro-inflammatory effects of iron coincide with the presence of positive results for synovial iron (III) using Perl's test and neutrophil infiltration. The results of this study suggest that the iron induced increase in synovitis in adjuvant arthritis is a result of iron promoted oxidative damage and is not likely to be due to the dextran C or the sorbitol citric acid components. It is suggested that a similar mechanism may occur in rheumatoid patients given iron supplements.