The impact of high lymphocyte sensitivity to glucocorticoids on kidney graft survival in patients treated with azathioprine and cyclosporine.
Lymphocyte sensitivity to methylprednisolone (MP) was examined in 70 consecutive cadaver kidney recipients: 36 recipients were given prednisolone and azathioprine (Aza), while 34 patients received prednisolone and cyclosporine (CsA). Peripheral blood lymphocytes (PBL) isolated just before transplantation, and again 6-12 hr after transplantation and i.v. administration of 120 mg of MP were stimulated with phytohemagglutinin (PHA). The observation period for all recipients was six months. In vivo, administration of MP was followed by a significant (P less than 0.02) decrease in the mitogen response of lymphocyte cultures from Aza-treated patients with graft function (n = 23) at six months. In contrast, the mitogen response of lymphocyte cultures from patients with graft failure (n = 13) did not decrease. Lymphocyte cultures from CsA-treated patients with graft function (n = 26) were not more responsive to i.v. MP than cultures from recipients who lost their grafts (n = 8). In vitro, the dose-response curves to MP were examined in pretransplant PHA cultures. The lymphocyte cultures from Aza-treated patients with graft function were 20 times more sensitive to MP than those of patients with graft failure at six months. The difference was highly significant (P = 0.005). Lymphocyte cultures from CsA-treated patients who maintained graft function were 12 times more sensitive to MP than cultures from recipients who lost their grafts (P = 0.02). Thus, in vivo and in vitro lymphocyte sensitivity to MP, which can be examined before transplantation, is suggested to have an important influence on the graft survival of azathioprine-treated patients. Furthermore, this effect is partly modified by treatment with cyclosporine.
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage*; D002478:Cells, Cultured; D016572:Cyclosporine; D003524:Cyclosporins / Q000008:administration & dosage* / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D015122:Mercaptopurine / Q000494:pharmacology; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D015122:Mercaptopurine; C050025:cyclosporin H; D001379:Azathioprine; D006854:Hydrocortisone; D008775:Methylprednisolone