Current status of FK 506 in liver transplantation.

Abstract

In 1987 Ochiai and coworkers presented a report on the immunosuppressive qualities of a new immunosuppressive agent, FK 506, isolated from the fermented broth of a soil fungus, Streptomyces tsukubaensis.1 Extensive in vitro studies demonstrated the effectiveness in suppressing mixed lymphocyte cultures, presumably by inhibiting 1L-2 synthesis following ailoactivation.2 The receptor for FK 506 has been identified and has been characterized as a peptidyl-prolyl cis-trans isomerasc.3 The background for the clinical development of FK 506 was well documented by Starzi in the opening remarks of a satellite symposium on FK 506, held in Barcelona, Spain, in November 1989 as part of the European Society of Organ Transplantation.4 In vivo studies using a number of animal models have shown a marked ability to prevent rejection following various types of organ transplants.5-7 More interestingly, FK 506 possesses the ability to reverse ongoing rejection in animal models.7,8 This characteristic is unique, since it is well known that cyclosporine (CyA) will not reverse established ongoing rejection. These properties served as the initiative to pursue clinical testing of FK506. The objective of this report is to update the reader on the current status of the use of FK 506 in liver transplantation at the University of Pittsburgh. One phase of the study consists of the “rescue” with FK 506 of liver allografts undergoing rejection with CyA-based immunosuppression.9 The second phase of the report consists of the results of primary liver transplantation using FK 506.10