gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Infliximab enhances intestinal regeneration and residual function following rescue therapy for acute cellular rejection (ACR) after rat small bowel transplantation

Meeting Abstract

  • Thomas Pech - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
  • Ichiro Ohsawa - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
  • Michael Praktiknjo - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
  • Tobias Finger - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
  • Kareem Abu-Elmagd - Thomas E. Starzl Transplantation Institute, Division of Intestinal Transplantation, Pittsburgh
  • Andreas Hirner - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
  • Jörg C. Kalff - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
  • Andreas Türler - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
  • Nico Schäfer - Universitätsklinikum Bonn, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch437

DOI: 10.3205/11dgch437, URN: urn:nbn:de:0183-11dgch4370

Published: May 20, 2011

© 2011 Pech et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: The small intestine is highly immunogenic and there is rising evidence that recurrent ACR episodes may trigger chronic rejection, having influence on the long term outcome. In previous studies, we established an experimental model to analyze the recovery and regeneration process after acute rejection. Infliximab is established in therapy of inflammatory bowel diseases, and it has been reported as successful rescue therapy for resistant rejection after small bowel transplantation. This study evaluated the effects of additional infliximab application during rescue therapy with tacrolimus basic immunosuppression to reveal mechanistical causes of this phenomenon.

Materials and methods: Orthotopic allogeneic intestinal transplantation was performed in rats. Immunosuppression with Tacrolimus 2 mg/kg/day was started on POD1 (group 1/continuous immunosuppression) or POD7 after manifestation of acute rejection. Animals were sacrificed on POD7 (group 2/acute rejection, no treatment), POD14 (group 3/immunosuppression) and POD21 (group 4/immunosuppression) during the recovery process. Additional infliximab treatment was administered on POD7 conjointly with tacrolimus. Animals were sacrified on POD14 (group 5/immunosuppression) or POD21 (group 6/immunosuppression).

Results: Tacrolimus and the combination therapy presented with steady, but not entirely, improved histological grading scores, accompanied by less leukocyte infiltration in the muscle layer (MPO-positive cells, 30%; infliximab/tacrolimus vs. tacrolimus only). mRNA-expression in the muscle layer revealed recovery in all groups treated with tracrolimus similar to combined treatment with infliximab. Enteric nerve recovery was enhanced by infliximab about 25% compared to tacrolimus only. Smooth muscle function improved from 60% (group 6) to 45% (group 4) reduction compared to non-transplanted controls.

Conclusion: Recovery from acute rejection progresses steady but slowly after starting immunosuppressive therapy as rescue therapy. Additional infliximab treatment enhances the physiological recovery of the muscle layer and enteric nervous system independent from inflammatory reactions. The improved smooth muscle function may prevent from postoperative ileus and possible successive bacterial overgrowth and translocation after small bowel transplantation.