Zhang G X, Baker C M, Kolson D L, Rostami A M
Department of Neurology, University of Pennsylvania Medical School, Philadelphia, PA 19104-4283, USA.
Mult Scler. 2000 Feb;6(1):3-13. doi: 10.1177/135245850000600103.
In recent years we have seen growing evidence for the role of chemokines in the pathogenesis of several infectious and non-infectious inflammatory CNS disease states, including Multiple Sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). An increase in proinflammatory chemokines has been associated with demyelinating lesions and clinical neurological dysfunction in patients with MS; these chemokines could be potential targets for MS therapy. Besides a clearly defined role in mediating leukocyte migration, these and other chemokines may act as immunoregulatory molecules in the driving to Th1/Th2 responses, switch of cytokine profiles, and the induction of tolerance. Since chemokine receptors have now been identified on macrophages, microglia, astrocytes, and endothelial cells as well as neurons in the CNS, chemokine/receptor interactions may mediate functional responses in a variety of CNS cell types during the course of inflammatory disease states. Therefore, clarification of the roles of chemokines and their receptors in the pathogenesis of EAE and MS will be useful in establishing immunotherapeutic strategies for these neurological autoimmune disorders.
近年来,我们越来越多地看到趋化因子在多种感染性和非感染性炎症性中枢神经系统疾病(包括多发性硬化症(MS)及其动物模型实验性变应性脑脊髓炎(EAE))发病机制中的作用证据。促炎趋化因子增加与MS患者的脱髓鞘病变和临床神经功能障碍有关;这些趋化因子可能是MS治疗的潜在靶点。除了在介导白细胞迁移中具有明确作用外,这些趋化因子以及其他趋化因子在驱动Th1/Th2反应、细胞因子谱转换和诱导耐受性方面可能作为免疫调节分子发挥作用。由于现已在中枢神经系统的巨噬细胞、小胶质细胞、星形胶质细胞、内皮细胞以及神经元上鉴定出趋化因子受体,趋化因子/受体相互作用可能在炎症性疾病过程中介导多种中枢神经系统细胞类型的功能反应。因此,阐明趋化因子及其受体在EAE和MS发病机制中的作用将有助于为这些神经自身免疫性疾病制定免疫治疗策略。