Gemcitabine--a novel immunosuppressive agent--prevents rejection in a rat cardiac transplantation model.
BACKGROUND
2',2' -difluorodeoxycytidine (dFdC, gemcitabine) is a pyrimidine antimetabolite with antineoplastic activity against a wide range of solid tumors. The immunosuppressive activities of this compound have not been described to date.


METHODS
The in vitro effects on activated T lymphocytes were studied with a lymphocyte colony-forming assay in a microagar culture system. Heart transplantations were performed in the fully allogeneic Lewis/ Brown Norway combination. dFdC was administered once daily at various dosages from the time of surgery until day 50.


RESULTS
Phytohemagglutinin-induced lymphocyte proliferation was inhibited 50% by dFdC at a concentration of 3.25+/-0.9 nmol/L. Allografts of untreated animals survived for 7.5 (7-8) days and those with 25, 50, and 75 microg/kg body weight dFdC for 7.3 (7-8), 9.3 (8-10), and 16.3 (10-38) days, respectively. Treatment with 100 or 125 microg/kg body weight of dFdC, however, prolonged allograft survival until day 152.8 (129-178). Dose-dependent leukopenia was the main toxicity.


CONCLUSIONS
DFdC is a new immunosuppressive agent that can successfully prevent cardiac rejection in a rat transplantation model.
Margreiter
R
R
Department of Transplant Surgery, Innsbruck University, Austria.
Fischer
M
M
Roberts
K
K
Schmid
T
T
Hittmair
A
A
Schirmer
M
M
Geisen
F
F
Tiefenthaler
M
M
Konwalinka
G
G
D000818:Animals; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000093542:Gemcitabine
D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D003841:Deoxycytidine; D000093542:Gemcitabine