FTY720 improves survival after transient ischemia and reperfusion of the hind limbs.
BACKGROUND
Ischemia and reperfusion (I/R) damage involves adhesion and transmigration of lymphocytes and neutrophils. FTY720 is an immunosuppressive agent that reduces the number of neutrophils and monocytes in peripheral blood as well as tissue lymphocyte infiltration. This study investigated the effect of FTY720 during hind limb I/R.


METHODS
Male C57/BL6 mice underwent temporary ligation of the infrarenal aorta for 4 hours. After 48 hours of reperfusion, animals were killed by exsanguination. Tissue myeloperoxidase content reflecting neutrophil infiltration and reverse transcription polymerase chain reaction analysis of local cytokine transcription in lung, liver, and kidney were performed.


RESULTS
After I/R, treatment with FTY720 improved survival and prevented upregulation of pro- and anti-inflammatory cytokines in evaluated organs, whereas no changes were detected in myeloperoxidase content after treatment with FTY720.


CONCLUSIONS
Whereas neutrophil infiltration was not affected by treatment with FTY720, other immunocompetent or intrinsic cells appear to be involved in changes of cytokine production in different organs.
Frink
Michael
M
Trauma Department, Hannover Medical School, Hannover, Germany. frink.michael@mh-hannover.de
Kaudel
Christian P
CP
Hildebrand
Frank
F
Pape
Hans-Christoph
HC
Klempnauer
Jürgen
J
Winkler
Michael
M
Krettek
Christian
C
van Griensven
Martijn
M
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D006614:Hindlimb / Q000098:blood supply; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D011336:Probability; D011409:Propylene Glycols / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000401:mortality*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015996:Survival Rate
D015415:Biomarkers; D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011409:Propylene Glycols; D009195:Peroxidase; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine