Effect of intravenous iron-dextran (Imferon) infusion on antigen induced monarticular arthritis in rabbits.

The effect of intravenously infused iron-dextran (Imferon) on the progression of antigen induced monarticular arthritis in rabbits was studied. A rapid deposition of iron and apoferritin in the synovia of arthritis joints occurred after infusion of iron-dextran during either the acute or chronic phases of the disease. This coincided with the appearance of catalytic (bleomycin reactive) iron in the synovial fluid. There was no evidence, however, for an exacerbation of the antigen induced arthritis as a result of the iron-dextran, and synovial and bleomycin reactive iron concentrations decreased with time after administration, indicating a redistribution of the synovial iron load. Thus although intravenously infused iron-dextran appears to 'prime' the rabbit arthritic joint transiently with the potential for iron stimulated oxygen free radical damage, other factors may determine its occurrence.

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.

Effect of nutritional iron deficiency on acute and chronic inflammation.

Mild nutritional iron deficiency significantly reduced the severity of adjuvant induced joint inflammation assessed by histology, microfocal radiography, and subjective scoring. Other indices of adjuvant induced inflammation, such as increased levels of serum acute phase reactants, characteristic pathological changes in the inguinal lymph nodes, and granuloma formation at the site of adjuvant injection, were not different from those of control animals. The level of iron deficiency used did not affect the acute inflammatory response to a range of irritants and was not sufficient to suppress immune function. Both the hypersensitivity reaction to oxazalone and lymphocyte tritiated thymidine incorporation were normal. These observations support the view that iron has a selective influence on joint mediated inflammation.

Effect of iron chelation on inflammatory joint disease.

Mild iron deficiency induced by treatment with the iron chelator desferrioxamine reduced the incidence and severity of joint inflammation associated with adjuvant disease in rats but did not alter the local primary inflammatory response or the systemic sequelae. Both rats treated with desferrioxamine and control rats showed increased levels of alpha 1 acid glycoprotein, characteristic pathological changes in the liver and inguinal lymph nodes, and the primary inflammatory response at the site of injection. Histology, microfocal radiography, and gross assessment of the joints, however, showed a suppression or reduction in soft tissue swelling and bone erosion in the rats treated with desferrioxamine. This is a novel observation suggesting an apparently selective influence of iron on joint mediated inflammation.

Protection of rams against epididymitis by a Brucella ovis-vitamin E adjuvant vaccine.

Rams vaccinated at 7 and 8 months of age with a B. ovis-vitamin E adjuvant vaccine had increased antibody titers compared with Freund's incomplete adjuvant or commercial bacterin vaccinated rams. The percent overall infectivity in an experimental infection of B. ovis-vitamin E adjuvant vaccinated rams was 22% compared to 44% for B. ovis-Freund's incomplete adjuvant or bacterin vaccinated rams and 67% for control.

Detection by electron microscope of rod-shaped organisms in synovial membrane from a patient with the arthritis of Whipple's disease.

Rod-shaped organisms identical to those present in the jejunal mucosa have been found in the synovial membrane of a patient with Whipple's disease. These probably caused inflammatory changes which sere reflected in an increase of the cellular content and high enzyme levels (acid phosphatase and 5-nucleotidase) of the synovial fluid. Tetracycline was effective in controlling the bowel lesion but only had a temporary effect upon the arthritis. Erythromycin controlled both the bowel lesion and the arthritis.