The effects of interleukin-1 receptor antagonist on oxidant-induced arthritis in mice.

OBJECTIVE

The anti-arthritic reactivity of the IL-1 receptor antagonist IL-1ra was tested in male DBA/1xB10A(4R) mice suffering from potassium peroxochromate-induced arthritis.

METHODS

Inflammatory arthritis was induced in male DBA/1xB10A(4R) mice by the intraplantar application of potassium peroxochromate and was quantified by the determination of the arthritis index, whole blood chemiluminescence, serum sulfhydryls and nitric oxides. Culture supernatants of the fibroblasts were assayed spectrophotometrically for collagenase release.

RESULTS

Overt arthritic symptoms, as measured by the arthritis index, were significantly inhibited after two intraperitoneal injections of 2 mg/kg IL-1ra. The phorbol-ester-stimulated chemiluminescent response of monocytes and polymorphonuclear leukocytes in whole murine blood, which increased 5-fold during the development of arthritis, was normalized to the level of healthy controls. The oxidation of serum sulfhydryls was inhibited by 25%, and the serum levels of nitric oxides was depressed by 40%. In vitro the IL-1-dependent induction of collagenase of rabbit synovial fibroblasts was completely suppressed in the presence of 0.4 mg/ml IL-1ra.

CONCLUSION

IL-1ra may prove useful to control the consequences of enhanced free radical production in inflammatory rheumatic diseases.