In vitro and in vivoimmunomodulatory effects of cobalt protoporphyrin administered in combinationwith immunosuppressive drugs
Academic Article
Publication Date:
2010
Short description:
In vitro and in vivoimmunomodulatory effects of cobalt protoporphyrin administered in combinationwith immunosuppressive drugs / Besenzon, F., Dedja, A., Vadori, M., Bosio, E., Seveso, M., Tognato, E., Polito, L., Calabrese, F., Valente, M., Rigotti, P., Ancona, E., Cozzi, E.. - In: TRANSPLANT IMMUNOLOGY. - ISSN 0966-3274. - 24:1(2010), pp. 1-8. [10.1016/j.trim.2010.08.002]
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).
CONCLUSION: Our in vitro and in vivo studies demonstrate that CoPP can potentiate the immunomodulatory effects of CsA, ultimately extending allograft survival.
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).
CONCLUSION: Our in vitro and in vivo studies demonstrate that CoPP can potentiate the immunomodulatory effects of CsA, ultimately extending allograft survival.
Iris type:
1.1 Articolo in rivista
List of contributors:
Besenzon, Federica; Dedja, Arben; Vadori, Marta; Bosio, Erika; Seveso, Michela; Tognato, E; Polito, L; Calabrese, Fiorella; Valente, Marialuisa; Rigotti, Paolo; Ancona, Ermanno; Cozzi, E.
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