Combined FTY720/cyclosporine A treatment promotes graft survival and lowers the peripheral lymphocyte count in DA to lewis heart and skin transplantation models

Transplant Immunology
Z NikolovaR P Hof

Abstract

The immunomodulator, FTY720, lowers the peripheral lymphocyte count (PLC) by inducing migration of circulating lymphocytes to secondary lymphoid organs. We investigated the efficacy of mono- vs. combined-FTY720/CsA therapy on graft survival (GS) and on lowering the PLC in a solid organ and a skin graft model, using strains with strong MHC disparity. Heterotopic cardiac or tail skin grafting was performed using the DA (RT1a) to Lewis (RT1(1)) rat strain combination. FTY720 was administered as a single daily dose by gavage alone or in combination with subcutaneously delivered CsA. PLC, body weight and drug concentrations were determined on day 7, 28, or the day of rejection. In placebo-treated animals the heart and skin allografts rejected after 6 and 8 days. FTY720 delayed rejection of both the solid organ and skin grafts. The maximal effect was achieved at 1 mg x kg(-l) x day(-1) FTY720, resulting in a median survival time (MST) of 14 days for both allotransplants comparable to the effect achieved by 1 mg x kg x day(-1) CsA in both models. In the cardiac graft experiment with CsA co-administration, doses of 0.3 and 1 mg/kg were used. Under these conditions very small doses of FTY720 were effective in maintaining grafts througho...Continue Reading

References

May 11, 1992·Transplantation·D H AdamsM J Karnovsky
Feb 1, 1969·The Journal of Thoracic and Cardiovascular Surgery·K Ono, E S Lindsey
Mar 20, 1999·Transplantation Proceedings·K YamashitaS Todo
Feb 9, 2000·Trends in Pharmacological Sciences·V BrinkmannL Feng

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Citations

Sep 17, 2013·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Yingfen YingJian Xu
Apr 10, 2009·Molecular Immunology·Thomas GruberGottfried Baier
Dec 6, 2003·Transplantation·Er-Ping ZhangFriedrich Hoffmann
Nov 28, 2007·American Journal of Clinical Dermatology·Thomas HerzingerHans Christian Korting
Nov 15, 2005·European Journal of Immunology·Margaret A MorrisKlaus Ley

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