• Jana Enderes, Julia van der Linde, Jan Müller, Bich-Thu Tran, Wolfram von Bernstorff, Claus-Dieter Heidecke, and Tobias Schulze.
• *Department of Surgery, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald,Germany †Department of Surgery, University Hospital of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany ‡Department of Immunology, Universitätsmedizin Greifswald, 17487 Greifswald, Germany §Department of Vascular Surgery, Krankenhaus Ludmillenstift, Ludmillenstraße 4-6, 49716 Meppen, Germany.
• Shock. 2016 Aug 24.

BackgroundFTY720 is an immunosuppressive molecule licensed for the treatment of chronic relapsing multiple sclerosis (MS). It attenuates the adaptive immune response by sequestering T cells within secondary lymphoid organs via its action as functional antagonist of sphingosine-1-phasphate. To date it is unknown whether FTY-induced lymphopenia puts MS patients at increased risk for severe forms of postoperative infectious complications such as abdominal sepsis.ObjectivesTo determine the effect of FTY720-induced lymphopenia on survival to sepsis secondary to postoperative intraabdominal infections in a murine model of polymicrobial sepsis.MethodsDetailed analysis of cellular dynamics in secondary lymphoid organs and of cytokine profiles was performed in FTY720-treated or placebo-treated C57BL/6 mice after induction of Colon ascendens stent peritonitis (CASP). Furthermore, survival analysis was performed in FTY720-treated and placebo-treated animals in severe CASP. Fifty per cent of each group were treated with broad spectrum antibiotics.ResultsFTY720 treatment resulted in remodelling of cell populations present in the peripheral blood, the peritoneal cavity and the spleen after CASP induction. Both lymphoid and myeloid cell lines were affected. However, survival in lymphopenic FTY720-treated animals was similar to placebo-treated mice following CASP. Antibiotic treatment increases survival in untreated as well as FTY720-treated animals to a similar extent.DiscussionOur data demonstrate that inhibition of T cell migration and induction of peripheral lymphopenia did not affect survival in a model of severe murine sepsis. The presence of reduced T- and B-cell numbers in the peripheral blood during a septic challenge did not negatively affect sepsis mortality in our model of severe abdominal sepsis. The absence of increased mortality under FTY720 treatment in the CASP model suggests that FTY720 treatment will probably not result in increased mortality in MS patients suffering from sepsis.

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