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.