2011 - ISBTS 2011 Symposium


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Oral Communications 10: Immune & Infectious Monitoring

11.223 - Effects of immunosuppressive therapy after experimental small bowel transplantation in rats

Presenter: Martin, von Websky, Bonn, Germany
Authors: Martin von Websky1, Thomas Pech1, Jun Fujishiro1, Tobias Finger1, Kareem Abu-Elmagd2, Joerg C. Kalff1, Nico Schaefer1

223
Effects of immunosuppressive therapy after experimental small bowel transplantation in rats

Martin von Websky1, Thomas Pech1, Jun Fujishiro1, Tobias Finger1, Kareem Abu-Elmagd2, Joerg C. Kalff1, Nico Schaefer1

1Department of Surgery, University of Bonn, Bonn, Germany; 2Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, United States

Background: Steady improvements of graft and patient survival were achieved over the past 20 years in the field of intestinal transplantation. Tacrolimus monotherapy with corticosteroids, or in combination with sirolimus is the most commonly used immunosuppressive regimen. Early after experimental allogenic small bowel transplantation in rats, sirolimus reduced the cellular and molecular inflammatory response with subsequent graft dysmotility more efficiently than tacrolimus, with contrary effects at 7 days after transplantation. This study evaluates three immunosuppressive strategies in the late phase after intestinal transplantation – tacrolimus or sirolimus monotherapy and the combination therapy of tacrolimus with infliximab.

Materials and Methods: After orthotopic intestinal transplantation between Brown Norway and Lewis rats, animals received 14 days immunosuppressive treatment. Histology, infiltration of neutrophils, monocytes and macrophages, cytokine and mediator mRNA expression (real time RT-PCR) and smooth muscle function in a standard organ bath were assessed at 14 days after transplantation in all treatment groups and isogenic controls. Allogenic transplanted rats without immunosuppressive therapy and non-transplanted animals served as further control.

Results: Tacrolimus prevented acute rejection and graft dysmotility more effectively (p≥0.05) compared to sirolimus. Reduced mRNA expression levels of CD4, IFN-γ, IL-6, IL-10, iNOS, NFκB, TNF-α and MCP-1 (p≤0.05) were observed in tacrolimus treated animals compared to sirolimus. Additional infliximab application did not influence the cellular and molecular inflammatory response in the late phase after transplantation.

Conclusions: The severe cellular and molecular inflammatory response in allogenic transplanted grafts without immunosuppressive therapy is ameliorated by all three immunosuppressive regimens, but tacrolimus presented more efficient than sirolimus at 14 days after transplantation. Our findings do not support the usage of sirolimus as single immunosuppressive therapy, but indicate and confirm the importance of tacrolimus as basic immunosuppressant in the field of intestinal transplantation.


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