title: Gemcitabine--a novel immunosuppressive agent--prevents rejection in a rat cardiac transplantation model.
abstract: 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.
authors.affiliation: Department of Transplant Surgery, Innsbruck University, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Margreiter
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: K
authors.initials: K
authors.lastname: Roberts
authors.forename: T
authors.initials: T
authors.lastname: Schmid
authors.forename: A
authors.initials: A
authors.lastname: Hittmair
authors.forename: M
authors.initials: M
authors.lastname: Schirmer
authors.forename: F
authors.initials: F
authors.lastname: Geisen
authors.forename: M
authors.initials: M
authors.lastname: Tiefenthaler
authors.forename: G
authors.initials: G
authors.lastname: Konwalinka
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D003841:Deoxycytidine; D000093542:Gemcitabine