Therapeutic activity of leflunomide in acute and chronic relapsing experimental allergic encephalomyelitis

We examined the therapeutic effect of leflunomide in the two models of acute and chronic relapsing EAE in Lewis rats. In the first model, sensitization of adult rats with guinea pig spinal cord resulted in an acute clinical episode of severe EAE, and by day 15 all animals died. Treatment of these sensitized Lewis rats with leflunomide was most effective in delaying and reducing the onset of clinical symptoms and mortality was prevented. The protection afforded by leflunomide was long-lasting and no subsequent relapse has been observed. In the second model of chronic relapsing EAE, aged Lewis rats (6–8 months old) were immunized with rabbit myelin basic protein, and all untreated animals developed a disease with up to three relapses. The second and third episodes were both milder and shorter in duration than the first. All animals treated with leflunomide survived the first attack, which was also delayed, in comparison to untreated controls, and relapses did not occur. Inhibition of pathological signs and prevention of relapses were observed even when leflunomide treatment was started after the first appearance of clinical symptoms of chronic relapsing EAE.