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-a was significantly higher in patients experiencing a rejection episode (941α83 pg/ml) than in those with a stable clinical course (240±6 pg/ml; P=0.004). Peak levels of TNF-α were usually found at the time of clinically diagnosed rejection, although elevated levels were observed 1-2 days earlier. First-week peak TNF-α 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-α 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-a levels were not elevated in four cases of viral hepatitis occurring after transplantation. We conclude that circulating levels of TNF-α are elevated during liver allograft rejection and may precede clinical manifestations. First-week TNF-α 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.