Evaluation of cytokines and cytokine-induced secondary messages in sera of patients after liver transplantation.

The study objective was first to investigate serum levels of tumor necrosis factor alpha, interleukin 1 beta, interferon gamma, interferon alpha, interleukin 2, beta-2-microglobulin (B2M), and urinary neopterin in patients after orthotopic liver transplantation; and second to relate their levels to clinical complications. The design used was the prospective observation study, and the setting used was the transplant unit of a university medical center. Serum samples were collected from 20 patients every alternate day from transplantation until discharge. The measurements and main results were as follows: concentrations of cytokines, B2M, and neopterin were performed using commercially available radioimmuno-assays. In seven out of nine patients with acute cellular rejections, elevated levels of TNF-alpha, IFN-gamma, IL-1, B2M, and neopterin were detected. The highest absolute levels of TNF-alpha were observed in patients with CMV disease. Increments in bacterial infections were comparable to those seen in the above-mentioned groups with the exception of IFN-gamma, which remained stable. IL-1 serum levels showed a different pattern with peak concentrations measured in sera before transplant and during rejection, while in the case of CMV disease levels gradually decreased. No detectable levels of IFN-alpha or IL-2 were observed. Our results indicate that enhanced endogenous production of TNF-alpha and IFN-gamma accompanied by elevated levels of B2M and neopterin represent a regular feature of inflammatory complications after liver transplantation. Serum cytokine levels however were not useful in distinguishing between rejection and infection. Evaluation of neopterin was more sensitive than cytokine or B2M measurement for the detection of inflammatory complications.