Intraoperative course and prognostic significance of endotoxin, tumor necrosis factor-alpha and interleukin-6 in liver transplant recipients.
Early events in reaction of the host immune system to an allograft were studied by intraoperative measurements of endotoxin (ET), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in human liver transplantation. Blood samples were collected prior to operation, before clamping of the liver vessels, at the beginning and end of the anhepatic phase, and 5 and 30 min after recirculation. Diagnosis of rejection and infection in the graft recipients was established by assessment of spontaneous blastogenesis and T-lymphocyte subpopulations in addition to clinical symptoms and results from biopsies and blood chemistry. Of the 27 unmatched liver transplantations included in this study, 8 patients had infections in the first two postoperative weeks and 6 patients showed rejection of their grafts under antithymocyte globulin immunoprophylaxis. Endotoxin was transiently elevated in plasma in the anhepatic phase (2-fold in comparison to normal values) as expected for an accumulation of intestine-derived endotoxin during clamping of liver vessels, but no correlation was found with TNF-alpha levels and specific post-transplant complications. All patients with rejections had high plasma levels of TNF-alpha immediately after recirculation (mean value 240 pg TNF-alpha/ml), in contrast to low TNF-alpha levels in graft recipients without complications or infections. These results indicate that the initiation of rejection in liver transplantation is associated with increased plasma concentrations of TNF-alpha. The measured TNF-alpha concentrations are adequate to promote the binding of lymphocytes to allograft endothelial tissue and/or to induce expression of MHC antigens in the graft. Subsequent viral or bacterial infections were preceded by high intraoperative plasma concentrations of interleukin-6 (mean value 1400 pg IL-6/ml). The correlations of rejection with high intraoperative TNF-alpha levels and of infection with those of IL-6 are statistically significant in Wilcoxon tests for the direct measurements and in Fisher's exact tests for positive test values, with limits of 90 pg/ml for TNF-alpha and 800 pg/ml for IL-6.
Hamilton
G
G
I. Surgical University Clinic, University School of Medicine, University of Vienna, Austria.
Prettenhofer
M
M
Zommer
A
A
Hofbauer
S
S
Götzinger
P
P
Gnant
F X
FX
Függer
R
R
D000328:Adult; D004731:Endotoxins / Q000097:blood*; D005260:Female; D006084:Graft Rejection; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007432:Intraoperative Period; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016031:Liver Transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013530:Surgical Wound Infection / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha