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

Transplant Proc. 2005 May;37(4):1929-30. doi: 10.1016/j.transproceed.2005.02.097.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Daclizumab
  • Graft Survival
  • Hepatocytes / cytology*
  • Hepatocytes / transplantation*
  • Immunoglobulin G / therapeutic use*
  • Immunosuppressive Agents / therapeutic use*
  • Liver Failure, Acute / surgery*
  • Male
  • Models, Animal
  • Rats
  • Rats, Inbred Lew
  • Rats, Wistar
  • Receptors, Interleukin-2 / immunology
  • Spleen
  • Transplantation, Homologous / immunology*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Interleukin-2
  • Daclizumab