IMMUNOMODULATION OF RAT ANTIGEN-INDUCED ARTHRITIS BY LEFLUNOMIDE ALONE AND IN COMBINATION WITH CYCLOSPORINE-A

The effects of the new immunomodulating isoxazol derivative leflunomid e, in comparison with cyclosporin A, on established antigen-induced ar thritis in rats as well as serum antibody levels were determined. When treatment with leflunomide, at concentrations from 2.5 to 10 mg/kg/d, was started on day 3 of arthritis, the acute and chronic phases of ar thritis were effectively inhibited. This was demonstrated by decreased joint swelling and reduced histopathological arthritis score at the e nd of experiment (day 26). Furthermore, the treatment resulted in a si gnificantly reduced level of serum antibodies to the matrix components collagen type I, type II and proteoglycans. Neither leflunomide nor c yclosporin A, at doses of 1 mg/kg/d, had an effect on the severity of arthritis and antibody levels. However, when both drugs were used toge ther, at these non-effective doses, the histopathological score of chr onic arthritis was significantly reduced. The results of our experimen ts demonstrate that leflunomide has a strong suppressive effect on bot h acute and chronic phases of antigen-induced arthritis and formation of autoantibodies in rats. Furthermore, orally administered doses of l eflunomide were as effective as doses of cyclosporin A given intraperi toneally. The combination of sub-effective doses of leflunomide and cy closporin A resulted in significant inhibition of chronic arthritis.