Preventive and therapeutic effects of cyclosporin and valine2-dihydro-cyclosporin in chronic relapsing experimental allergic encephalomyelitis in the Lewis rat

Abstract

Cyclosporin (CS) and valine2-dihydro-cyclosporin [(Val2)DH-CS] were tested in adult Lewis rats with chronic relapsing experimental allergic encephalomyelitis (CR-EAE), induced by the immunization of guinea-pig spinal cord emulsified in complete Freund's adjuvant. The drugs were given orally for 15 or 35 days, at 12.5, 25 or 50 mg/kg/day, starting either on the day of sensitization (preventive treatment) or at one of three subsequent times (therapeutic treatment): the onset of the first attack (protocol A); the onset of the first spontaneous remission (protocol B); and the onset of the second attack (protocol C). Used therapeutically in protocol A, at doses above 12.5 mg/kg/day, both drugs prolonged remission past the end of therapy in more than two-thirds of the treated animals, compared to less than 10% of controls. Trends were similar under protocols B and C. Disease developing after preventive treatment with either drug was predominated by chronic and hyperacute attacks, in contrast to the relapsing course of controls. This pattern was also the result after CS was given therapeutically, whereas (Val2)DH-CS in such circumstances eliminated all further attacks in the majority of rats (58-86% at 25 mg/kg/day) and only minimal disease occurred in the remainder. We conclude that both drugs, in this model, are beneficial during administration; however, in contrast to CS, (Val2)DH-CS possesses an important, curative action when applied therapeutically.