title: In vitro and in vivo immunomodulatory effects of cobalt protoporphyrin administered in combination with immunosuppressive drugs.
abstract: BACKGROUND
  Immunosuppressive strategies are designed to take advantage of potential synergies between drugs to possibly decrease the risk of side-effects. In the present study, the ability of Cobalt protoporphyrin (CoPP) to potentiate the effect of the immunosuppressive drugs mycophenolate sodium (MPS) or cyclosporin A (CsA) was explored in vitro and in vivo.
  
  
  METHODS
  In vitro analyses of proliferation and apoptosis were performed on primate T cell cultures, following incubation with the immunosuppressive drugs MPS or CsA, alone or in combination with CoPP. In vivo the effect of CoPP and CsA combination therapy was assessed in a rat heterotopic cardiac allotransplantation model.
  
  
  RESULTS
  In vitro results suggest that co-administration of CoPP with CsA or MPS increases immunosuppressive effects of these drugs when combined with CoPP. In particular, the co-administration of CoPP with CsA resulted in the synergistic induction of lymphocyte apoptosis. In vivo, animals immunosuppressed with CsA (1.5 mg/kg) or CoPP (20 mg/kg) alone, had a median survival of 7 or 8 days, respectively. In contrast, animals immunosuppressed with CsA (1.5 mg/kg) combined with CoPP (20 mg/kg) had significantly prolonged median survival (12 days), compared to recipients treated with CsA or CoPP alone (p<0.05).
  
  
  CONCLUSIONS
  Our in vitro and in vivo studies demonstrate that CoPP can potentiate the immunomodulatory effects of CsA, ultimately extending allograft survival.
authors: Department of Surgical and Gastroenterological Sciences, University of Padua, Ospedale Giustinianeo, Padua, Italy. federica.besenzon@unipd.it
authors: Federica
authors: F
authors: Besenzon
authors: Arben
authors: A
authors: Dedja
authors: Marta
authors: M
authors: Vadori
authors: Erika
authors: E
authors: Bosio
authors: Michela
authors: M
authors: Seveso
authors: Elena
authors: E
authors: Tognato
authors: Luigino
authors: L
authors: Polito
authors: Fiorella
authors: F
authors: Calabrese
authors: Marialuisa
authors: M
authors: Valente
authors: Paolo
authors: P
authors: Rigotti
authors: Ermanno
authors: E
authors: Ancona
authors: Emanuele
authors: E
authors: Cozzi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000008:administration & dosage; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011524:Protoporphyrins / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D016572:Cyclosporine; D009173:Mycophenolic Acid