Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation – a pilot study. (15th March 2013)

• Record Type: Journal Article
• Authors: Hautz, Theresa; Krapf, Christoph; Grahammer, Johanna; Zelger, Bettina; Hickethier, Tilman; Seger, Christoph; Eberhart, Nadine; Wallner, Christoph; Messner, Franka; Kotsch, Katja; Griesmacher, Andrea; Brandacher, Gerald; Lee, WP Andrew; Margreiter, Raimund; Pratschke, Johann; Glossmann, Hartmut; Schneeberger, Stefan
• Is Part Of: Transplant international. Volume 26:Number 5(2013:May)
• Page Start: 552
• Page End: 561
• Publication Date: 2013-03-15
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95405
• DOI: 10.1111/tri.12080
• Languages: English
• ISSNs: 0934-0874

Abstract

<abstract abstract-type="main" xml:lang="en" id="tri12080-abs-0001"> <title>Summary</title> <p>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.</p> </abstract>