使用α4整合素小分子抑制剂长期逆转慢性实验性变应性脑脊髓炎

Prolonged reversal of chronic experimental allergic encephalomyelitis using a small molecule inhibitor of alpha4 integrin.

作者信息

Piraino P S, Yednock T A, Freedman S B, Messersmith E K, Pleiss M A, Vandevert C, Thorsett E D, Karlik S J

机构信息

Department of Physiology, London Health Sciences Center, University of Western Ontario, London, ON, Canada.

出版信息

J Neuroimmunol. 2002 Oct;131(1-2):147-59. doi: 10.1016/s0165-5728(02)00273-4.

DOI:10.1016/s0165-5728(02)00273-4

PMID:12458046

Abstract

CNS leukocytic invasion in experimental allergic encephalomyelitis (EAE) depends on alpha4beta1 integrin/vascular cell adhesion molecule-1 (VCAM-1) interactions. A small molecule inhibitor of alpha4beta1 integrin (CT301) was administered to guinea pigs in the chronic phase (>d40) of EAE for 10, 20, 30 or 40 days. CT301 elicited a rapid, significant improvement in the clinical and pathological scores that was maintained throughout the treatment period. A progressive loss of cells in the spinal cord of treated animals confirmed the resolution of inflammation associated with clinical recovery. Therefore, prolonged inhibition of alpha4beta1 integrin caused a sustained reversal of disease pathology in chronic EAE and may be similarly useful in MS.

摘要

实验性自身免疫性脑脊髓炎（EAE）中中枢神经系统（CNS）的白细胞浸润依赖于α4β1整合素/血管细胞黏附分子-1（VCAM-1）的相互作用。在EAE的慢性期（>40天），将α4β1整合素的小分子抑制剂（CT301）给予豚鼠，持续给药10、20、30或40天。CT301使临床和病理评分迅速、显著改善，且在整个治疗期间维持这种改善。治疗动物脊髓中的细胞逐渐减少，证实了与临床恢复相关的炎症消退。因此，长期抑制α4β1整合素可使慢性EAE的疾病病理持续逆转，在多发性硬化症（MS）中可能同样有效。