Arsenic trioxide attenuated the rejection of major histocompatibility complex fully-mismatched cardiac allografts in mice.
We investigated the effects of arsenic trioxide (As(2)O(3)) 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 As(2)O(3)-treated group, intraperitoneal (IP) injection of As(2)O(3) (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 As(2)O(3) plus CsA-treated group, a combined protocol of As(2)O(3) 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 As(2)O(3)-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 As(2)O(3)-treated group. Allografts of As(2)O(3)-treated and As(2)O(3) plus CsA-treated mice showed a changing pattern of Th1/Th2 cytokine mRNA expression. Allograft rejection was apparently alleviated by low-dose As(2)O(3), and particularly when combined with a subtherapeutic CsA dose.
Yan
S
S
Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, China.
Zhang
Q Y
QY
Zhou
B
B
Xue
L
L
Chen
H
H
Wang
Y
Y
Zheng
S S
SS
D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006131:Growth Inhibitors / Q000627:therapeutic use; D016027:Heart Transplantation / Q000276:immunology*; D006650:Histocompatibility Testing; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010087:Oxides / Q000627:therapeutic use*; D014184:Transplantation, Homologous / Q000276:immunology
D001152:Arsenicals; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D010087:Oxides; D016572:Cyclosporine; D000077237:Arsenic Trioxide