Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation

In human orthotopic liver transplantation (LTX) intraoperative elevations of TNF-α (> 100 pg/ml) and IL-6 (>800 pg/ml) have been found to correlate with early post-operative rejections and infections respectively. In this study the possible mechanism responsible for the induction of these cyto...

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Main Authors: Gerhard Hamilton, Sonja Vogel, Reinhold Fuegger, Franz X. M. Gnant
Format: Article
Language:English
Published: Hindawi Limited 1993-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/S0962935193000420
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spelling doaj-3bab41256f67477fb868360c6afcec4d2020-11-24T21:11:11ZengHindawi LimitedMediators of Inflammation0962-93511466-18611993-01-012430330710.1155/S0962935193000420Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantationGerhard Hamilton0Sonja Vogel1Reinhold Fuegger2Franz X. M. Gnant3Department of Surgery, University School of Medicine, Alserstr. 4, Vienna A-1090, AustriaDepartment of Surgery, University School of Medicine, Alserstr. 4, Vienna A-1090, AustriaDepartment of Surgery, University School of Medicine, Alserstr. 4, Vienna A-1090, AustriaDepartment of Surgery, University School of Medicine, Alserstr. 4, Vienna A-1090, AustriaIn human orthotopic liver transplantation (LTX) intraoperative elevations of TNF-α (> 100 pg/ml) and IL-6 (>800 pg/ml) have been found to correlate with early post-operative rejections and infections respectively. In this study the possible mechanism responsible for the induction of these cytokines has been investigated during liver allografting in 38 recipients. Intraoperative elevations of TNF-α (> 100 pg/ml) were detected in the majority of pre-transplant endotoxin positive recipients (8/12, > 10 endotoxin units/ml), the patients turning endotoxin positive until the end of grafting (3/5), and in a subgroup (6/21 patients), apparently endotoxin negative for the whole operation. Therefore endotoxin (ET) seems to stimulate release of TNF-α in approximately 50% of the patients, whereas sensitized Kupffer graft cells or immediate allograft reactivity of the host are likely to account for the remaining TNF-α positive cases. Elevations of IL-6 > 800 pg/ml) were found in approximately 50% of the TNF-α positive cases, indicating partially independent regulatory pathways for IL-6 induction in the TNF-α negative patients. In agreement with a previous study, 11/13 (85%) of the intraoperative TNF-α positive recipients rejected their grafts within the first 10 days post-operatively. These data demonstrate that ET/infection associated as well as ET independent/reperfusion associated intraoperative TNF-α elevations, promote the initiation of allograft rejection in human liver transplantation. The transient and low endotoxaemia caused by the liver grafting procedure performed without veno-venous bypass seems to be of minor importance in the intraoperative induction of TNF-α.http://dx.doi.org/10.1155/S0962935193000420
collection DOAJ
language English
format Article
sources DOAJ
author Gerhard Hamilton
Sonja Vogel
Reinhold Fuegger
Franz X. M. Gnant
spellingShingle Gerhard Hamilton
Sonja Vogel
Reinhold Fuegger
Franz X. M. Gnant
Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation
Mediators of Inflammation
author_facet Gerhard Hamilton
Sonja Vogel
Reinhold Fuegger
Franz X. M. Gnant
author_sort Gerhard Hamilton
title Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation
title_short Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation
title_full Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation
title_fullStr Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation
title_full_unstemmed Mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation
title_sort mechanisms of tumor necrosis factor-α and interleukin-6 induction during human liver transplantation
publisher Hindawi Limited
series Mediators of Inflammation
issn 0962-9351
1466-1861
publishDate 1993-01-01
description In human orthotopic liver transplantation (LTX) intraoperative elevations of TNF-α (> 100 pg/ml) and IL-6 (>800 pg/ml) have been found to correlate with early post-operative rejections and infections respectively. In this study the possible mechanism responsible for the induction of these cytokines has been investigated during liver allografting in 38 recipients. Intraoperative elevations of TNF-α (> 100 pg/ml) were detected in the majority of pre-transplant endotoxin positive recipients (8/12, > 10 endotoxin units/ml), the patients turning endotoxin positive until the end of grafting (3/5), and in a subgroup (6/21 patients), apparently endotoxin negative for the whole operation. Therefore endotoxin (ET) seems to stimulate release of TNF-α in approximately 50% of the patients, whereas sensitized Kupffer graft cells or immediate allograft reactivity of the host are likely to account for the remaining TNF-α positive cases. Elevations of IL-6 > 800 pg/ml) were found in approximately 50% of the TNF-α positive cases, indicating partially independent regulatory pathways for IL-6 induction in the TNF-α negative patients. In agreement with a previous study, 11/13 (85%) of the intraoperative TNF-α positive recipients rejected their grafts within the first 10 days post-operatively. These data demonstrate that ET/infection associated as well as ET independent/reperfusion associated intraoperative TNF-α elevations, promote the initiation of allograft rejection in human liver transplantation. The transient and low endotoxaemia caused by the liver grafting procedure performed without veno-venous bypass seems to be of minor importance in the intraoperative induction of TNF-α.
url http://dx.doi.org/10.1155/S0962935193000420
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