Effect of LS-2616 on the graft protection achieved by cyclosporin A, prednisolone, and 15-deoxyspergualin in heart-transplanted rats.
The immunostimulator LS-2616 abolishes the effect of cyclosporin A in a rat cardiac transplantation model. The present paper compares the characteristics of rejection obtained under different immunosuppressive regimens with and without additional LS-2616 application in the same model. Cyclosporin A (CyA, 10 mg/kg daily), prednisolone (15 mg/kg daily), or 15-deoxyspergualin (2, 5, or 10 mg/kg daily), all given from the day of transplantation until day 9, protected the grafts during the treatment period. The addition of LS-2616 (160 mg/kg, day -1 until stop) resulted in a total abrogation of the immunosuppressive effect of CyA and prednisolone. However, LS-2616 could only partially or not at all reverse the effect of 15-deoxyspergualine. These results show a certain drug selectivity of LS-2616 in promoting rejection of immunosuppressed allografts. Further studies with LS-2616 may be of benefit in evaluating the mode of action of different immunosuppressive compounds and, thus, contribute to finding more effective antirejection therapies.
Wanders
A
A
Department of Pathology, University Hospital, Uppsala, Sweden.
Gannedahl
G
G
Gerdin
B
B
Tufveson
G
G
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006146:Guanidines / Q000627:therapeutic use*; D016027:Heart Transplantation / Q000276:immunology*; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D023421:Models, Animal; D011239:Prednisolone / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013997:Time Factors
D000276:Adjuvants, Immunologic; D006146:Guanidines; D006912:Hydroxyquinolines; D007166:Immunosuppressive Agents; C045282:roquinimex; D016572:Cyclosporine; D011239:Prednisolone; C037258:gusperimus