Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients

Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disord er in which the central nervous system (CNS) inflammatory reaction is large ly restricted to mononuclear phagocytes and T cells. We asked whether speci fic chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of thr ee chemokines that act toward T cells and mononuclear phagocytes: interfero n-gamma-inducible protein. of 10 kDa (IP-10); monokine induced by interfero n-gamma (Mig); and regulated on activation, normal T-cell expressed and sec reted (RANTES). We then investigated whether specific chemokine receptors w ere expressed by infiltrating cells in demyelinating MS brain lesions and i n CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, an d microglia in actively demyelinating MS brain lesions. Compared with circu lating T cells, CSF T cells were significantly enriched for cells expressin g CXCR3 or CCR5. Our results imply pathogenic roles for specific chemokine- chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.