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  • Title: Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation - a pilot study.
    Author: Hautz T, Krapf C, Grahammer J, Zelger B, Hickethier T, Seger C, Eberhart N, Wallner C, Messner F, Kotsch K, Griesmacher A, Brandacher G, Lee WP, Margreiter R, Pratschke J, Glossmann H, Schneeberger S.
    Journal: Transpl Int; 2013 May; 26(5):552-61. PubMed ID: 23489391.
    Abstract:
    Kv1.3-channels are critically involved in activation and function of effector memory T cells. Blocking Kv1.3-channels was investigated for its effect on skin rejection in a rat limb-transplantation-model. Animals received the Kv1.3-blocker correolide C systemically or locally as intra-graft-treatment in combination with tacrolimus. Systemic (intraperitoneal) administration of correolide C resulted in slight, but significant prolongation of allograft survival compared with untreated and placebo treated controls. In 4/6 correolide C treated animals, histology showed an intact epidermis and a mild infiltrate by day 10. High correolide C plasma trough levels correlated with prolonged allograft survival. A decrease in CD4+ and CD8+ effector memory T cells was observed in allograft skin, peripheral blood and the spleen on day 5. When applied subcutaneously in combination with systemic tacrolimus (30 days+/-anti-lymphocyte serum) detectable, but insignificant prolongation of graft survival was achieved. 2/5 animals showed an intact epidermis and a mild infiltrate until day 45. Tapering systemic tacrolimus and weaning on day 50 resulted in rejection by day 55, regardless of local correolide C treatment. Subcutaneous injection did not lead to systemic plasma levels. The Kv1.3-channel is a potential drug target worth exploring in more detail for immunosuppression in vascularized composite allotransplantation.
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