A short course of FK506 can induce limited donor-specific graft acceptance.
To examine the hypothesis that a short course of FK506 would induce permanent graft acceptance after lung transplantation, left lung allotransplantation was performed in 14 mongrel dogs. In group 1 (control; n = 3), no immunosuppressive agent was given. In group 2 (n = 7), FK506 (1.2 mg/kg intramuscularly) was given on posttransplantation days 0, 1, and 2. In group 3 (n = 4), FK506 was given at the same dose on posttransplantation days 0, 1, and 2 as well as on days 29 and 30. Allograft function was evaluated by temporarily occluding the right pulmonary artery. A mixed lymphocyte reaction study was performed preoperatively and monthly thereafter. Control lungs were all rejected within 8 days. Group 2 dogs showed improved survival, with a median survival of 49.5 days. One dog in group 2 lived more than 400 days after transplantation. The mixed lymphocyte reaction data suggests that some donor-specific unresponsiveness occurs, which lasts for only a limited time. Supplemental doses of FK506 did not significantly improve survival (median, 74 days). The whole blood level of FK506 was 17.7 +/- 3.98 ng/mL on day 15; however, on day 29 the FK506 level was almost undetectable. We conclude that a 3-day course of 1.2 mg/kg of FK506 can induce donor-specific graft acceptance, but this acceptance is not permanent.
Hirai
T
T
Department of Thoracic Surgery, Kyoto University, Japan.
Waddell
T K
TK
DeCampos
K N
KN
Compeau
C G
CG
Wada
H
H
Hitomi
S
S
Patterson
G A
GA
Slutsky
A S
AS
D000818:Animals; D004285:Dogs; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
D016559:Tacrolimus