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The use of FK-506 for small intestine llotransplantation: Inhibition of acute rejection and prevention of fatal graft-versus-host disease

Hoffman, AL and Makowka, L and Banner, B and Cai, X and Cramer, DV and Pascualone, A and Todo, S and Starzl, TE (1990) The use of FK-506 for small intestine llotransplantation: Inhibition of acute rejection and prevention of fatal graft-versus-host disease. Transplantation, 49 (3). 483 - 490. ISSN 0041-1337

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Abstract

Small intestine allotransplantation in humans is not yet feasible due to the failure of the current methods of immunosuppression. FK-506, a powerful new immunosuppressive agent that is synergistic with cyclosporine, allows long-term survival of recipients of cardiac, renal, and hepatic allografts. This study compares the effects of FK-506 and cyclosporine on host survival, graft rejection, and graft-versus-host-disease in a rat small intestine transplantation model. Transplants between strongly histoincompatible ACI and Lewis (LEW) strain rats, and their Fi progeny are performed so that graft rejection alone is genetically permitted (F1→LEW) or GVHD alone permitted (LEW→F < inf > 1 < /inf > ) or that both immunologic processes are allowed to occur simultaneously (ACI—»LEW). Specific doses of FK-506 result in prolonged graft and host survival in all genetic combinations tested. Furthermore, graft rejection is prevented (ACI→LEW model) or inhibited (rejection only model) and lethal acute GVHD is eliminated. Even at very high doses, cyclosporine did not prevent graft rejection or lethal GVHD, nor did it allow long-term survival of the intestinal graft or the host. Animals receiving low doses of cyclosporine have outcomes similar to the untreated control groups. No toxicity specific to FK-506 is noted, but earlier studies by other investigators suggest otherwise. © 1990 by Williams & Wilkins


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hoffman, AL
Makowka, L
Banner, B
Cai, X
Cramer, DV
Pascualone, A
Todo, S
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1990
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 49
Number: 3
Page Range: 483 - 490
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062110980, Starzl CV No. 1057
Date Deposited: 08 Apr 2010 17:18
Last Modified: 13 Oct 2017 23:01
URI: http://d-scholarship.pitt.edu/id/eprint/4443

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