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Ann Thorac Surg 1994;58:496-501
© 1994 The Society of Thoracic Surgeons

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Articles

A short course of FK506 can induce limited donor-specific graft acceptance

^a Department of Thoracic Surgery, Chest Disease Research Institute, Kyoto University, Kyoto, Japan
^b Division of Thoracic Surgery, Department of Surgery, University of Toronto, Toronto Hospital, Toronto, Ontario, Canada

Accepted for publication December 22, 1993.

^_* Address reprint requests to Dr Slutsky, Respiratory Medicine, Mount Sinai Hospital. 600 University Ave, Ste 656A, Toronto, Ont M5C 1X5 Canada.

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 donorspecific graft acceptance, but this acceptance is not permanent.

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