多発性硬化症におけるケモカインシグナル伝達系の検討

Multiple sclerosis(MS)is an inflammatory demyelinating disease of the central nervous system and one of the earliest changes in inflammatory focus involves the activation of vascular endothelial cells.We determined the plasma level of plasminogen activator inhibitor-1(PAI-1)，a key regulator of fibrinolysis and cell migration，in patients with MS.The level of plasma PAI-1was significantly higher in active MS cases when compared to stable MS and controls.Plasma concentrations of tissue plasminogen activator，transforming growth factor beta-1，and lipoprotein-a remained normal in spite of disease activity。These results suggested that PAI-1 plasma levels are associated with MS disease activity and is a good marker for MS relapse.Expression of chemokine receptors on lymphocytes in blood and cerebrospinal fluid(CSF)of active multiple sclerosis(MS)patients were analyzed at pre-and post-intravenous methylprednisolone(IVMP)therapy.Both CD 4 I D 1+I D 1 and CD 8 I D 1+I D 1 cells in CSF at the relapse were enriched for CXCR3 and CCR5(Th1 Chemokines)expression，and were reduced for CCR4(Th2 Chemokine)expression compared with blood.CCR1 and CCR2 expression was also altered in MS patients。After IVMP therapy，CCR5expression was reduced in CSF CD4 I D1+I D1 cells.These results suggest that biased Th1/Th2 balance plays a role for active disease process and CCR5expression on CSF CD4 I D1+ii D1 cells is a good marker of the disease activity.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and one of the earliest changes in inflammatory focus involves the activation of vascular endothelial cells. We determined the plasma level of plasminogen activator inhibitor-1(PAI-1), a key regulator of fibrinolysis and cell migration, in patients with MS. The level of plasma PAI-1 was significantly higher in active MS cases when compared to stable MS and controls. Plasma concentrations of tissue plasminogen activator, transforming growth factor beta-1, and lipoprotein-a remained normal in spite of disease activity. These results suggested that PAI-1 plasma levels are associated with MS disease activity and is a good marker for MS relapse. Expression of chemokine receptors on lymphocytes in blood and cerebrospinal fluid (CSF) of active multiple sclerosis (MS) patients were analyzed at pre- and post-intravenous methylprednisolone (IVMP) therapy. Both CD4ィイD1+ィエD1 and CD8ィイD1+ィエD1 cells in CSF at the relapse were enriched for CXCR3 and CCR5 (Th1 chemokines) expression, and were reduced for CCR4 (Th2 chemokine) expression compared with blood. CCR1 and CCR2 expression was also altered in MS patients. After IVMP therapy, CCR5 expression was reduced in CSF CD4ィイD1+ィエD1 cells. These results suggest that biased Th1/Th2 balance plays a role for active disease process and CCR5 expression on CSF CD4ィイD1+ィエD1 cells is a good marker of the disease activity.