Pretransplantation tumor necrosis factor-alpha production predicts acute rejection after liver transplantation

Abstract

Immunosuppressive therapy has many adverse effects in both the short and longer term. Tailoring immunosuppression might be possible if pretransplantation parameters predicted rejection. We investigated production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokine, interleukin-10 (IL-10), pretransplantation to determine whether there is a relation with acute rejection. Peripheral-blood mononuclear cells were obtained from patients with chronic liver disease on the waiting list for orthotopic liver transplantation and healthy controls. Cells (0.5 x 10(6)) were stimulated with 200 ng of lipopolysaccharide. Preincubation for 30 minutes with tacrolimus, cyclosporine, and dexamethasone at concentrations of 10 and 100 ng was also performed. TNF-alpha and IL-10 levels were measured by enzyme-linked immunosorbent assay. Acute rejection was defined on clinical and histological grounds. Pretransplantation in vitro production of TNF-alpha significantly (P <.05) increased in the group of patients with acute rejection (n = 9) compared with those who did not develop rejection (n = 12). Preincubation with dexamethasone significantly (P <.001) reduced TNF-alpha and IL-10 production in both patients and controls (n = 8). IL-10 production pretransplantation was not different in those who developed acute rejection (n = 9) compared with those who did not (n = 9). Preincubation with tacrolimus augmented (P <.05) the production of IL-10 in patients (n = 18), but not controls (n = 6). Pretransplantation TNF-alpha production is increased in patients who go on to develop acute rejection posttransplantion.