15 AU81, a prostacyclin analog, potentiates immunosuppression and mitigates renal injury due to cyclosporine.
15 AU81, a synthetic prostacyclin analog, inhibits human mixed lymphocyte culture responses in a dose-dependent manner at concentrations within a range [0.1 to 10.0 micrograms/ml] similar to that of cyclosporine, methylprednisolone, antilymphocyte serum, and prostaglandin E1 and E2 analogs. Using the median-effect analysis to dissect immunosuppressive interactions, 15 AU81 and cyclosporine were shown to produce synergistic effects on human peripheral blood lymphocyte activation upon phytohemagglutinin or anti-CD3 monoclonal antibody stimulation. In vivo, 15 AU81 potentiated the effect of cyclosporine to prolong the survival of rabbit renal allografts using concentrations of each agent that were individually ineffective. Furthermore, addition of 15 AU81 mitigated functional damage of rabbit kidneys due to high-dose cyclosporine therapy. These observations suggest that the addition of 15 AU81 may broaden the therapeutic window of cyclosporine by potentiating immunosuppression and mitigating nephrotoxic effects.
Division of Immunology and Organ Transplantation, University of Texas, Houston 77030.
L J
LJ
Dumble
S
S
Gibbons
N
N
Tejpal
T C
TC
Chou
N G
NG
Redgrave
M J
MJ
Boyle
B D
BD
Kahan
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D004357:Drug Synergism; D006085:Graft Survival / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D016030:Kidney Transplantation; D008954:Models, Biological; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D011817:Rabbits
D011465:Prostaglandins, Synthetic; C054809:U 62840; D016572:Cyclosporine