Successful orthotopic small bowel transplantation with short-term FK 506 immunosuppressive therapy.

A LTHOUGH small bowel transplantation is the physiologic treatment of the short bowel syndrome, Its clinical implementation awaits development of immunosuppressive regimens that ensure satisfactory control of graft rejection. Agents such as Cy A and corticosteroids are useful for transplantation of most other vascularized organ allografts. However, rejection of the transplanted small intestine has been found more difficult to prevent. probably because the large lymphoid content of the intestine renders it more immunogenic and because the bamer function of the intestine magnifies defects in immunosuppression that would otherwise be inconsequential in transplantation of other organs. Prolonged and, in some instances, indefinite survival of small bowel allografts using CyA has been demonstrated in several large and small animal models. However. in clinical small bowel transplantation. <~5'7c long-term functional graft survival has been achieved when CyA has been used as the primary immunosuppressive agent (Grant D, personal communication. October 1989). demonstrating the need for other more effective immunosuppressive agents. The macrolide FK 506 has been shown to have potent in vitro and in vivo immunosuppressive activity and to delay rejection of kidney. I heart. C and Ii ver' allografts in a number of experimental animal models. The effectiveness of FK 506 has also recently been reported in clinical liver and kidney transplantatio~." To determine whether FK 506 can effectively prevent the rejection of small bowel allografts. studies were undertaken in a rat model of small bowel transplantation.