Evidence that LS-2616 (linomide) causes acute rejection of rat allografts protected by cyclosporine but not of long-term surviving allografts
1991 (English)In: Transplantation, Vol. 52, no 2, 234-8 p.Article in journal (Refereed) Published
The immunomodulator LS-2616 (Linomide) induces rejection of cyclosporine-protected rat cardiac allografts. The aim of this study was to characterize this rejection in the presence of CsA and to test LS-2616 in other models of permanent graft acceptance in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto (Wi/Ky) rat recipients on day 0. The recipients were treated orally on days 0-9 with CsA (10-40 mg/kg) and/or with LS-2616 (2.5-160 mg/kg) starting at different times (day -7 -+5) until the day of complete rejection. The addition of LS-2616 (day -1--stop) to CsA (10 mg/kg) resulted in a dose-dependent antagonism of the immunosuppressive effect of CsA with daily doses of 2.5-160 mg/kg. Furthermore, the results were similar, irrespective of whether LS-2616 treatment (160 mg/kg) was started on day -7, -1, +1, +3, or +5. LS-2616 (160 mg/kg) pretreatment of the recipient for 7 days before transplantation was considerably less effective. CsA (20 mg/kg) for 14 days after a PVG to DA transplantation resulted in permanent graft survival. This was not abrogated by LS-2616. Neither was rejection induced in long-term surviving grafts of RT1.C incompatible Lewis recipients. Our data suggest that LS-2616 activates already stimulated and sensitized T cells that are otherwise controlled by CsA.
Place, publisher, year, edition, pages
1991. Vol. 52, no 2, 234-8 p.
Animals, Cyclosporins/*pharmacology, Dose-Response Relationship, Drug, Drug Administration Schedule, Graft Rejection/*drug effects, Graft Survival/*drug effects, Heart Transplantation/physiology, Hydroxyquinolines/*adverse effects, Immunohistochemistry, Kidney Transplantation/physiology, Male, Myocardium/pathology, Rats, Rats, Inbred Strains, Rats, Inbred WKY, Time Factors, Transplantation, Homologous/physiology
IdentifiersURN: urn:nbn:se:umu:diva-110952ISBN: 0041-1337 (Print) 0041-1337 (Linking)OAI: oai:DiVA.org:umu-110952DiVA: diva2:865822
Wanders, A Vogt, P Karlsson-Parra, A Wonigkeit, K Gerdin, B Tufveson, G eng Research Support, Non-U.S. Gov't 1991/08/01 Transplantation. 1991 Aug;52(2):234-8.2015-10-292015-10-292015-10-29