The role of tumor necrosis factor in allograft rejection. I. Evidence that elevated levels of tumor necrosis factor-alpha predict rejection following orthotopic liver transplantation.
Plasma levels of tumor necrosis factor-alpha were measured in 50 adult patients following orthotopic liver transplantation. The mean (+/- SEM) plasma concentration of TNF-alpha was significantly higher in patients experiencing a rejection episode (941 +/- 83 pg/ml) than in those with a stable clinical course (240 +/- 6 pg/ml; P = 0.0001). Peak levels of TNF-alpha were usually found at the time of clinically diagnosed rejection, although elevated levels were observed 1-2 days earlier. First-week peak TNF-alpha levels were significantly higher in patients who suffered graft loss (2146 +/- 788 pg/ml) than in those who were discharged from the hospital without clinical evidence of rejection (581 +/- 93 pg/ml; P = 0.004). TNF-alpha levels were not correlated with white blood cell count (r2 = 0.004), cyclosporine levels (0.01), serum creatinine (0.002), serum bilirubin (0.05), serum SGOT (0.03), or SGPT (0.05). TNF-alpha levels were not elevated in four cases of viral hepatitis occurring after transplantation. We conclude that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. First-week TNF-alpha levels are also useful predictors of long-term graft outcome. Further investigation is required to determine whether this monokine is important in the actual pathogenesis of allograft rejection.
Imagawa
D K
DK
Department of Surgery, University of California, Los Angeles School of Medicine 90024.
Millis
J M
JM
Olthoff
K M
KM
Derus
L J
LJ
Chia
D
D
Sugich
L R
LR
Ozawa
M
M
Dempsey
R A
RA
Iwaki
Y
Y
Levy
P J
PJ
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D003524:Cyclosporins / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection; D006801:Humans; D007958:Leukocyte Count; D016031:Liver Transplantation / Q000276:immunology*; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin