Lipoprotein-induced modulation of cyclosporine-A-mediated immunosuppression.
Human serum lipoproteins form complexes with cyclosporine-A and act as a carrier of cyclosporine-A in vivo. We compared the immunosuppressive effects of free cyclosporine-A, a complex composed of cyclosporine-A and lipoproteins, free cyclosporine-A in the presence of each unbound lipoprotein, and each lipoprotein without cyclosporine-A with one another at concentrations comparable with in vivo conditions on PHA-stimulated peripheral blood mononuclear cells. Free cyclosporine-A reduced the proliferation of the PHA-stimulated mononuclear cells to 50% at a concentration of 300 ng ml-1 (SD +/- 30, n = 12) lipoprotein-deficient medium. Cyclosporine-A loaded into VLDL showed a 50% proliferation rate reduction at 60 micrograms VLDL ml-1 (SD +/- 10, n = 12) and 180 ng cyclosporine-A ml-1. In the presence of 100 ng ml-1 cyclosporine-A 180 micrograms ml-1 VLDL (SD +/- 25, n = 12) showed a proliferation rate reduction of 50%. In the same way VLDL without cyclosporine-A induced a reduction to 50% at 740 micrograms ml-1 (SD +/- 30, n = 12). Cyclosporine-A loaded into LDL showed a 50% proliferation rate reduction at 27 micrograms ml-1 LDL (SD +/- 5, n = 12) with 80 ng ml-1 cyclosporine-A. In the presence of 100 ng ml-1, cyclosporine-A 150 micrograms ml-1 LDL (SD +/- 25, n = 12) showed a proliferation rate reduction of 50%. In the same way, LDL without cyclosporine-A induced a reduction to 50% at 950 micrograms ml-1 (SD +/- 50, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)
Rödl
S
S
Department of Medical Biochemistry, Karl-Franzens-University of Graz, Austria.
Fuchs
G
G
Khoshsorur
G
G
Iberer
F
F
Tscheliessnigg
K H
KH
D003524:Cyclosporins / Q000008:administration & dosage*; D004337:Drug Carriers; D006801:Humans; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000008:administration & dosage*; D008075:Lipoproteins, HDL / Q000008:administration & dosage; D008077:Lipoproteins, LDL / Q000008:administration & dosage; D008079:Lipoproteins, VLDL / Q000008:administration & dosage; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology
D003524:Cyclosporins; D004337:Drug Carriers; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010835:Phytohemagglutinins