FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia in C57/BL6 mice.
BACKGROUND
Organ dysfunction followed by single-organ or even multiorgan failure due to ischemia-reperfusion injury (I/RI) is a common problem in liver and heart transplantation. Various approaches had been attempted to prevent this I/RI. One is the administration of FTY720, a synthetic structural analogue of sphingosine, which induces T-lymphocyte homing with consecutive lymphopenia. The purpose of this study was to evaluate the effect of intraoperative FTY720 administration following controlled bilateral kidney ischemia in comparison to steroid or placebo application.


METHODS
Male c57BL6/J mice (n = 115; body weight 25 to 30 g) received either FTY720 (1 mg/kg body weight) or steroids or saline solution. Ischemia was applied for 30 or 60 minutes with subsequent follow-up for 48 hours. At termination all surviving animals were sacrificed.


RESULTS
Following 30 minutes of ischemia, FTY720, but neither steroid nor vehicle treatment showed significant protective effects on long-term survival after controlled bilateral warm kidney ischemia. Fluorescein-activated cell sorting (FACS) analysis showed a significant T-lymphocyte depletion in peripheral blood after FTY720 treatment, which was not observed after steroid or vehicle treatment.


CONCLUSIONS
The improved long-term survival shown in this study might be due to a protective effect of FTY720 to prevent I/RI, which may be mediated by the lymphocyte depletion shown in the FACS analysis.
Kaudel
C P
CP
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany. kaudel.philipp@mh-hannover.de
Schmiddem
U
U
Frink
M
M
Bergmann
S
S
Pape
H-C
HC
Krettek
C
C
Klempnauer
J
J
Winkler
M
M
D000818:Animals; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000517:prevention & control*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine