Gadolinium chloride suppresses acute rejection and induces tolerance following rat liver transplantation by inhibiting Kupffer-cell activation

The aim of the present study was to investigate the mechanism by which gadolinium chloride (GdCl 3 ) inhibits Kupffer cell (KC) activation and its ability to suppress acute rejection and induce tolerance following liver transplantation in rats. Rats were randomly divided into control, liver transplantation with GdCl 3 pretreatment and liver transplantation with normal saline pretreatment groups. The survival rate, liver function, hepatic pathological histology, cytokine levels in the liver and bile, activity of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in KCs, and expression levels of membranous molecules on the KCs were observed. It was identified that the one-month survival rate in the GdCl 3 group was significantly higher compared with that in the saline group (P<0.05). The liver function in the GdCl 3 group gradually recovered following transplantation surgery; however, it progressively deteriorated in the saline group. There were minor changes of hepatic pathological histology in the GdCl 3 group, whereas changes typical of acute rejection occurred in the saline group. In the GdCl 3 group, the levels of interferon γ and interleukin (IL)-2 were significantly lower whereas the levels of IL-10 were significantly higher compared with those in the control and saline groups (all P<0.01). The IL-4 levels in the GdCl 3 and control groups were similar. The activity of NF-κB in the saline group was significantly higher compared with those in the control and GdCl 3 groups (P<0.01). The expression levels of major histocompatibility complex-II, cluster of differentiation (CD)80 and CD86 on the KC membranes in the GdCl 3 group was significantly lower compared with those in the control group (P<0.05); however, these membranous proteins were highly expressed in the saline group. These data indicate that GdCl 3 efficiently inhibits the immunological activity of KCs, suppresses acute rejection and induces tolerance following liver allograft transplantation in rats.