Prolongation of heart allograft survival in rats by interferon-specific antibodies and low dose cyclosporin A.
Interferons (IFNs) are important cytokines which exhibit antiviral, antitumor, anticellular, as well as immunoregulatory activities. Among these multiple activities, IFNs are potent inducers of MHC antigen expression of a great variety of cells, helper and maturation factors in B-cell antibody production, and macrophage function. IFNs may therefore play a critical role in triggering antigen recognition and allograft rejection. Cyclosporin A (CyA) is a potent immunosuppressor which selectively inhibits helper T-lymphocyte proliferation in response to alloantigen presentation. CyA has been reported to inhibit interleukin 2 and IFNgamma production by helper T lymphocytes. In addition, CyA may induce monocyte production of prostaglandin E2, which then reduces MHC class II expression on endothelial cells, monocytes, and macrophages. However, the clinical use of CyA is plagued by its toxic (in particular nephrotoxic) side-effects. These toxic effects are clearly dose-related. It may be very important to develop new products which can act synergistically with CyA to inhibit lymphokine production. The aim of this study was to investigate the effects of combined IFN-specific antibodies and low dose CyA on cardiac allografts in inbred strains of rats.
Gugenheim
J
J
Laboratoire de Recherches Chirurgicales et Service de Chirurgie Digestive, Hôpital Saint-Roch, Nice Cedex 1, France.
Tovey
M
M
Gigou
M
M
Crafa
F
F
Fabiani
B
B
Reynes
M
M
Bismuth
H
H
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000918:Antibody Specificity; D016572:Cyclosporine / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007372:Interferons / Q000276:immunology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013997:Time Factors; D014184:Transplantation, Homologous
D000906:Antibodies; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007372:Interferons