Low-dose cyclosporine maintenance therapy after immunosuppressive induction in a rat cardiac transplant model.
An immuno-reduction-suppression protocol using spleen cell infusion followed by cyclophosphamide (CP) or azathioprine (AZ) to reduce the immunocompetent cells and maintenance suppression with low-dose cyclosporine (CsA) was highly effective in a rat cardiac transplant model. Following one or two spleen cell infusions, AZ or CP treatment was given before transplantation. After transplantation the animals were maintained with low-dose CsA. Among those treated with AZ, five of eight survived greater than 100 days, and among those treated with CP, six of eight survived greater than 100. These two protocols were far superior to 28 other permutations of treatment consisting of 164 transplants, such as infusions plus AZ without CsA and infusions without AZ but with CsA. We conclude that CsA can most effectively be used in low dose as a maintenance drug and that immunoreduction therapy is optimized by prestimulation and expansion of reactive cells. Another important feature of this proposal is that the immunoreductive risk phase, performed before transplantation, can be separated from the operative risk period. This avoids the conventional superimposition of the two risks.
Takiff
H
H
Department of Surgery, UCLA School of Medicine, Los Angeles, CA 90024.
Novak
M
M
Iwaki
Y
Y
Terasaki
P I
PI
D000818:Animals; D001379:Azathioprine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003524:Cyclosporins / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D007165:Immunosuppression Therapy / Q000379:methods*; D008297:Male; D008954:Models, Biological; D011184:Postoperative Period; D011300:Preoperative Care; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D013154:Spleen / Q000637:transplantation; D013156:Splenectomy; D014184:Transplantation, Homologous / Q000401:mortality
D003524:Cyclosporins; D003520:Cyclophosphamide; D001379:Azathioprine