P-glycoprotein functions in peripheral-blood CD4+ cells of patients with systemic lupus erythematosus.
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 (Rh123) 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, i.e., 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.
Henmi
Kayo
K
Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. y984164@educ.ps.toyaku.ac.jp
Yoshida
Masaharu
M
Yoshikawa
Noriko
N
Hirano
Toshihiko
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005456:Fluorescent Dyes; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D012235:Rhodamines
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000893:Anti-Inflammatory Agents; D017252:CD3 Complex; D005456:Fluorescent Dyes; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012235:Rhodamines; D016572:Cyclosporine; D011241:Prednisone