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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor.
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Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor.

机译：通过cAMP特异性磷酸二酯酶抑制剂预防非人类灵长类动物自身免疫脱髓鞘。

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摘要

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.
机译：实验性过敏性脑脊髓炎（EAE）是中枢神经系统的自身免疫性疾病，可作为人类疾病多发性硬化症的模型。我们评估了咯利普兰（IV型磷酸二酯酶抑制剂）在预防普通mar猴Callithrix jacchus中EAE的功效。在一个盲目的实验设计中，在两只人接受安慰剂治疗的动物中，在用人白质免疫后的17天内，出现了EAE的临床体征，但在免疫后1周开始的三只猴子中，没有接受过咯利普兰（隔日10 mg / kg sc）的任何一只猴子。在对照中，EAE的体征与脑脊液的细胞增多和脑MRI异常有关。在治疗组中，只有三只动物中的一只得到了持续的保护，免受临床EAE，短暂性脑脊髓液细胞增多，MRI无异常以及组织病理学发现明显减少的影响。咯利普兰治疗的动物和对照动物同样会产生针对髓鞘碱性蛋白的循环抗体。因此，对中枢神经系统抗原致敏后开始的对IV型磷酸二酯酶的抑制作用可防止自身免疫性脱髓鞘疾病。

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