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129. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

24.04. - 27.04.2012, Berlin

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Graft tolerance and immunological consequence following a combined THI / Prograf® substitution after liver transplantation in the rat: a novel immunsuppresant drug

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  • Edouard Matevossian - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München
  • Arno Kornberg - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München
  • Anne Preissel - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München
  • Stefan Thorban - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München
  • Jörg Nährig - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München
  • Daniel Reim - Klinikum Rechts der Isar München, Chirurgische Klinik und Poliklinik, München

Deutsche Gesellschaft für Chirurgie. 129. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 24.-27.04.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgch062

doi: 10.3205/12dgch062, urn:nbn:de:0183-12dgch0628

Published: April 23, 2012

© 2012 Matevossian 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

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Introduction: Acute rejection is still a common complication of liver transplantation (LTx). CD4 /CD8 T cells represent a subpopulation of T lymphocytes, and are a marker for allograft rejection. It is known that lymphocyte regress after allograft transplantation depends on sphingosine 1-phosphate (S1P) receptor-1. Treatment with 2-Acetyl-4-tetra-hydroxybutyl imidazole (THI) inhibits the S1P-degrading enzyme and plays a fundamental role in the immune response. The aim of this experimental study is to evaluate the protective effects with mono- or Prograf®-combined THI treatment of the recipients after LTx in a rat model.

Materials and methods: Arterialised orthotopic allogeneic liver transplantation was performed in LEWIS/DA . The recipients are divided into 4 groups: group I (controls without THI or Prograf® pre-treatment/immunosuppression of the recipients, n=6); group II (immunsuppression of the recipients (day 0-28 after LTx) with high-dose Prograf®, n=6); group III (pre-treatment of the recipients (day 0-28 after LTx) with THI, n=6); group IV (pre-treatment and immunosuppression of the recipients (day 0-28 after LTx) with low-dose Prograf® and day 0-14 after LTx with THI, n=8).

Results: Our preliminary data (FACS) with application of a single THI-injection 90 minutes before liver transplantation show a significant decrease of CD4 /CD8 populations of the T-lymphocytes in the recipients peripheral blood and liver allograft (p= 0.002, group III vs. group I). The histopathologic evaluation of the grafts showed regarding to the number of necrotic areas a significant difference between the group I (mean 11,2) vs. group III (mean 4.2) and group IV (mean 1.6), p= 0.0013. The middle maximal size of these areas differs significant between group I (mean 5.2 mm) and group IV (mean 0.22 mm, p=0.002).

Conclusion: These experimental results show that the immunological consequence following a combined THI/Prograf® substitution after LTx has an organ protective effect to the graft and gives credence to the theory that the reduction of T-lymphocytes before reperfusion will prevent or reduce acute rejection episodes in liver allografts.