Lublin F D, Lavasa M, Viti C, Knobler R L
Clin Immunol Immunopathol. 1987 Oct;45(1):122-8. doi: 10.1016/0090-1229(87)90118-8.
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.
研究了抗肿瘤免疫调节剂米托蒽醌对小鼠急性和复发性实验性变态反应性脑脊髓炎（EAE）病程的影响。未治疗的免疫小鼠产生急性EAE的临床疾病发病率为81%，病理疾病发病率为100%。在免疫后的10天内，每天以0.5mg/kg的剂量用米托蒽醌治疗的小鼠未出现任何临床症状，且疾病的病理症状轻微。0.25mg/kg的剂量产生了中等反应。未治疗的免疫复发性EAE的小鼠疾病发病率为100%，平均发病时间为第148天。在免疫后的12周内，每周三次以0.05mg/kg的剂量用米托蒽醌治疗的小鼠临床疾病发病率为67%，平均发病日期显著延迟至第279天。这些结果表明，米托蒽醌在抑制急性EAE的发展方面非常有效。米托蒽醌延迟了小鼠复发性EAE的发病，但并未完全抑制疾病的最终表现。这些研究表明，在自身免疫性疾病的治疗中使用细胞毒性疗法可能需要周期性的治疗周期来阻断疾病的表现。
