Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis.
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.
Zhang
G X
GX
Department of Neurology, University of Pennsylvania Medical School, Philadelphia, PA 19104-4283, USA.
Baker
C M
CM
Kolson
D L
DL
Rostami
A M
AM
D018925:Chemokines / Q000276:immunology*; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology* / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology*
D018925:Chemokines; D019707:Receptors, Chemokine