Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone

The effect of treatment with the antineoplastic, immunomodulatory agent mitoxantrone on the course of acute and relapsing experimental allergic encephalomyelitis (EAE) in the mouse has been studied. Untreated mice immunized to produce acute EAE had an 81% incidence of clinical disease and 100% incidence of pathologic disease. Mice treated with mitoxantrone at a dose of 0.5 mg/kg daily for the 10 days following immunization did not develop any clinical signs and had minimal pathologic signs of disease. A dose of 0.25 mg/kg gave an intermediate response. Untreated mice immunized for relapsing EAE had a 100% incidence of disease with an average onset of disease on Day 148. Mice treated with mitoxantrone at a dose of 0.05 mg/kg three times weekly for 12 weeks following immunization had a 67% incidence of clinical disease with a significant delay in the average onset date to Day 279. These results indicate that mitoxantrone was highly effective in suppressing development of acute EAE. Mitoxantrone delayed the onset of relapsing EAE in mice, but did not fully inhibit the eventual expression of the disease. These studies suggest that the use of cytotoxic therapies in the treatment of autoimmune diseases may require periodic cycles of therapy to block disease expression.