Arsenic Trioxide Attenuated the Rejection of Major Histocompatibility Complex Fully-Mismatched Cardiac Allografts in Mice

We investigated the effects of arsenic trioxide (As2O3) on allogeneic immune response using a mouse heart transplantation model. Mice were randomly divided into 4 groups of 6 animals each. The control group received phosphate-buffered saline (PBS); the As2O3-treated group, intraperitoneal (IP) injection of As2O3 (1 mg/kg) from days −3 to 10 after heart transplantation. The cyclosporine (CsA)-treated group was given a subtherapeutic dose of CsA (10 mg/kg) IP, and the As2O3 plus CsA-treated group, a combined protocol of As2O3 and CsA. Six days after transplantation, cardiac allografts were harvested for immunohistology and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The survival of the allografts was significantly improved among the As2O3-treated group compared with the control group (17.2 ± 1.9 vs 8.0 ± 0.9 days; P < .05). A marked prolongation (28.6 ± 6.0 days) of graft survival was achieved by the combined protocol compared with the CsA-treated group (9.6 ± 3.0 days; P < .05) or the As2O3-treated group. Allografts of As2O3-treated and As2O3 plus CsA-treated mice showed a changing pattern of Th1/Th2 cytokine mRNA expression. Allograft rejection was apparently alleviated by low-dose As2O3, and particularly when combined with a subtherapeutic CsA dose.