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


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.


CONCLUSIONS
This experimental model showed the safe, effective use of Dmab.
Tsiolis
I
I
Department of Surgery, E. Dynan Hospital, Athens, Greece.
Papalois
A
A
Loukopoulos
I
I
Gravvanis
A
A
Lykoudis
E
E
Theodossopoulou
E
E
Chairakakis
A
A
Dimitroulopoulos
D
D
Sfiniadakis
I
I
Vassiliou
I
I
Felekouras
E
E
Dedeilias
P
P
Kontogiorgi
M
M
Papadimitriou
L
L
Papadimitriou
I
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D006085:Graft Survival; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017114:Liver Failure, Acute / Q000601:surgery*; D008297:Male; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013154:Spleen; D014184:Transplantation, Homologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D000077561:Daclizumab