Prolonged survival of rat hepatic allografts treated with a pretransplant donor-specific blood transfusion is associated with reduced cytokine-induced neutrophil chemoattractant expression

Background. One intravenous injection of freshly heparinized donor blood 7 days before transplantation significantly prolongs hepatic allograft survival from ACI (RT1(a)) to LEW (RT1(1)) rats. The aim of this study was to investigate hepatic allograft expression of neutrophil chemoattractant and tumor necrosis factor in immunologic unresponsiveness. Methods and Results. Cytokine-induced neutrophil chemoattractant levels in untreated hepatic allografts were significantly higher than in allografts treated with donor-specific transfusion. Additionally, more neutrophils infiltrated untreated than transfusion-treated hepatic allografts. The number of chemoattractant-positive cells was significantly lower in donor-specific transfused allografts than in untreated hepatic allografts. The number of ED1(+) mononuclear cells infiltrating portal areas of untreated allografts increased over time and expressed abundant cytokine-induced neutrophil chemoattractant mRNA during acute rejection. This correlated with significantly higher levels of chemoattractant mRNA in untreated allograft livers on postoperative day 5 as compared with transfusion-treated allografts. Serum concentrations of tumor necrosis factor-alpha in untreated hepatic allograft recipients increased over time and peaked on day 7, while those in transfused allografts were maintained at lower levels. Moreover, in vitro chemoattractant production by peritoneal macrophages responded in a dose-dependent manner to tumor necrosis factor-alpha. Conclusion. Donor-specific transfusion treatment decreases tumor necrosis factor-alpha and chemoattractant expression as well as neutrophil accumulation in hepatic allografts.