Experimental isolation and transplantation of hepatocytes with the use of antibody against interleukin-2 receptor (daclizumab) as immunosuppressive agent.

INTRODUCTION: Daclizumab (Dmab) is a genetically engineered humanized IgG1 monoclonal antibody that binds to the alpha chain of the interleukin-2 receptor (Tac, CD25, p55) expressed on activated human T lymphocytes. Dmab has been used in a clinical protocol of islet transplantation with satisfactory results. The aim of the present study was to evaluate the use of an antibody against the interleukin-2 receptor (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte allotransplantation (allo-Tx) in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 48 Lewis rats as recipients: four groups of 12 animals each with induction of FHF and 24 hour later hepatocyte Tx--group A: no treatment; group B: cyclosporin (20 mg/kg days 0 to 5 and 10 mg/kg days 6 to 15); group C: Dmab (0.05 mg day of Tx and 0.05 mg day 7); and group D: Dmab and cyclosporine. Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: Statistical analysis showed better survival among groups C (83%, MST = 13) and D (92%, MST = 14.25) compared to groups A (max 72, MST = 1.5) or B (50%, MST = 9). Survival in group D was better but not significantly than group C. Biochemical evaluation and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model showed the safe, effective use of Dmab.

Use of mycophenolate mofetil in the experimental allo-transplantation of hepatocytes in rats with fulminant hepatic failure.

AIM: The aim of the study was to evaluate the beneficial effect of mycophenolate mofetil (MMF) as an immunosuppressive agent for experimental transplantation of hepatocytes in rats with fulminant hepatic failure (FHF). MATERIALS AND METHODS: Six Wistar rats were used as donors and 40 Lewis rats at recipients, including four groups of 10 animals each. Group A received no treatment; Group B, cyclosporine (20 mg/kg days 0-5 and 10 mg/kg days 6-15); Group C, MMF (12 mg/kg per os every day); and Group D, MMF (23 mg/kg per os every day). Hepatocytes were transplanted intrasplenically. Animals were followed for 15 days. RESULTS: The survival rates for Group A were maximum 72 h, whereas Groups B, C, and D showed 50%, 70%, and 80%, respectively. Biochemical evaluation and histology showed satisfactory function and engraftment, respectively. CONCLUSION: The use of MMF in this experimental model yielded safe, satisfactory immunosuppression especially at the dose of 23 mg/kg.