Prolonged lung allograft survival with a short course of FK 506.
We examined the hypothesis that FK 506 would induce graft acceptance after lung transplantation. Left lung allotransplantation was performed in size-matched mongrel dogs allocated to control (no immunosuppression, n = 3) and FK 506 (n = 5) groups. FK 506 (1.2 mg/kg intramuscularly every day) was given on posttransplantation days 0, 1, and 2. No other immunosuppressive agents were administered to either group. Chest x-ray and transplant lung physiologic assessments were performed on the fifth day and weekly thereafter. On day 29 an open lung biopsy and a third-party skin graft were performed. Lymphocytes were harvested and frozen from the recipient peripheral blood before transplantation and on days 8 and 29 afterwards for assessment in mixed lymphocyte reaction. Dogs were killed when their chest x-ray films showed allograft opacification or when the skin graft was rejected. Control lungs were all rejected after a median of 5 days. In the FK 506 group, one of five dogs aspirated during the fifteenth-day assessment and was killed, on the twenty-ninth day, because of severe rejection. At day 29, in the other four dogs, the transplanted lung yielded an arterial oxygen tension of 613 +/- 25 mm Hg (mean +/- standard deviation) and lung biopsy specimens showed no abnormalities histologically. These four dogs rejected third-party skin grafts after a median of 10 days. In two FK 506 dogs, mixed lymphocyte reaction at day 8 showed suppression of proliferation responses against donor and third-party lymphocytes. By day 29 responses against third-party lymphocytes had returned to almost preoperative levels, whereas antidonor responses were still suppressed. After skin graft rejection and killing, one of four dogs showed no sign of rejection, and the other three showed minimal to mild lung rejection at the time they were killed. We conclude that a 3-day course of 1.2 mg/kg of FK 506 induced prolonged graft acceptance after lung transplantation in dogs.
Hirai
T
T
Department of Surgery, University of Toronto, Toronto General Hospital, Ontario, Canada.
Waddell
T K
TK
Puskas
J D
JD
Wada
H
H
Hitomi
S
S
Gorczynski
R M
RM
Slutsky
A S
AS
Patterson
G A
GA
D000818:Animals; D001663:Bilirubin / Q000097:blood; D001706:Biopsy; D001784:Blood Gas Analysis; D003208:Concanavalin A; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D006439:Hemodynamics; D007273:Injections, Intramuscular; D007958:Leukocyte Count; D016040:Lung Transplantation / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D008176:Lung Volume Measurements; D007959:Lymphocyte Culture Test, Mixed; D011652:Pulmonary Circulation; D011859:Radiography; D016038:Skin Transplantation / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D003208:Concanavalin A; D003404:Creatinine; D001663:Bilirubin; D016559:Tacrolimus