P-Glycoprotein Functions in Peripheral-Blood CD4^+ Cells of Patients with Systemic Lupus Erythematosus(Pharmacology)

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Over-expression of P-glycoprotein (P-gp) in lymphocytes is implicated in the failure of immunosuppressant therapy. We investigated P-gp function in peripheral-blood CD3^+, CD4^+, and CD8^+ cells of 14 healthy subjects and 12 patients with systemic lupus erythematosus (SLE). P-gp function was estimated by the transporter activity of the cells based on the efflux of Rhodamine-123 (Rhl23) from the cells in the presence or absence of a P-gp inhibitor, cyclosporine A. P-gp function in the CD8^+ cells of the healthy subjects was significantly higher than that of the SLE patients (p=0.0318), whereas the function in CD3^+ cells and CD4^+ cells were not significantly different between the healthy subjects and the SLE patients. The patients were divided into two subgroups according to their clinical response to glucocorticoid (GC) therapy, Le., a high-response group (HR) (n=6) and a low-response group (LR) (n=6). In contrast, P-gp function in CD4^+ cells of the LR group was significantly higher than that of the HR group (p=0.0432). Further, no significant differences in the P-gp function in CD3^+ and CD8^+ cells were observed between the two groups. The data showed a relationship between clinical sensitivity to GC therapy and P-gp function of CD4^+ cells in SLE patients. Thus, the estimation of P-gp function in peripheral-blood CD4^+ cells might be useful for the estimation of clinical response to GC therapy.
公益社団法人日本薬学会の論文
2008-05-01