title: Phase-directed therapy and cardiac xenograft survival.
abstract: Xenotransplant rejection is facilitated not only by T cell upregulation but also by endothelial activation and B cell/antibody mechanisms, which standard immunosuppression is unable to overcome and xenorejection ensues. However, therapy directed specifically at each phase of xenorejection may improve xenograft survival. To study this we used a heterotopic cardiac xenotransplant mode (Syrian hamster to Lewis rat). Controls had no immunotherapy. Xenorecipients received cyclosporine to restrict T cellular response/development or cyclophosphamide, an antiproliferative, to reduce xenoreactive clones and antibody/complement injury, or anti-TNF antibody to alter cytokine cascades and endothelial activation/inflammation. Further xenorecipients received combinations. While single modalities alone did not enhance survival, combinations appeared to be at least additive in vivo, suggesting that therapy directed at specific phases of xenorejection may prove useful.
authors.affiliation: Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109, USA.
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: B R
authors.initials: BR
authors.lastname: Gastman
authors.forename: R Q
authors.initials: RQ
authors.lastname: Wei
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: D
authors.initials: D
authors.lastname: Gordon
authors.forename: S F
authors.initials: SF
authors.lastname: Bolling
mesh_terms: D000818:Animals; D006224:Cricetinae; D003520:Cyclophosphamide / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous
chemical_list: D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide