gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Interleukin-33 prolongs allograft survival during chronic cardiac rejection

Meeting Abstract

  • Stefan Brunner - Universitätsklinik Regensburg, Chirurgie, Regensburg
  • Gabriela Schiechl - Universitätsklinik Regensburg, Chirurgie, Regensburg
  • Hans Jürgen Schlitt - Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg
  • Stefan Fichtner-Feigl - Universitätsklinik Regensburg, Chirurgie, Regensburg

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch554

DOI: 10.3205/11dgch554, URN: urn:nbn:de:0183-11dgch5540

Veröffentlicht: 20. Mai 2011

© 2011 Brunner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: IL-33 stimulates the generation of cells and cytokines characteristic of a T-helper-2 immune response, whereas T-helper-1/17 immune responses are capable of mediating cardiac allograft rejection. In this study, we demonstrate the effect of IL-33 on allograft function during chronic cardiac rejection in mice.

Materials and methods: B6.C-H2bm12/KhEg hearts were transplanted into MHC-II-mismatched C57BL/6J mice. Graft function was assessed by palpation. Starting at day 5 IL-33 was administered i.p. daily. Cardiac allografts were harvested, graft infiltrating cells were isolated and cytokine production was determined by ELISA. Cells isolated from allografts and spleens were analysed by flow cytometry. Further immunohistochemistry was performed.

Results: Control animals showed allograft rejection within 22 days after transplantation in contrast to IL-33 treated animals with an allograft survival of 48 days. This clinically obvious effect of reduced allograft rejection could also be verified by H&E staining. The prolonged allograft survival following IL-33 treatment was due to a significant decrease in the production of pro-inflammatory IL-17A and significantly increased levels of the Th2-cytokines IL-5, IL-10 and IL-13. In addition, IL-33 treatment resulted in changes in the lymphoid and myeloid compartment in both the cardiac allografts and the periphery. FACS analyses demonstrated a relative reduction of CD4+ T-cells in the allograft by 30%, whereas the relative level of CD8+ T-cells remained unchanged. Amongst CD4+ T-cells a significant increase of CD4+ Foxp3+ Treg could be detected. A significant decrease in CD11bhighGr1high granulocytes coinciding with a significant increase in CD11bhighGr1intermediate myeloid cells could be observed in cardiac allografts, as well as in the periphery.

Conclusion: IL-33 treatment prolongs cardiac allograft survival in mice. IL-33 induces changes in cytokine production of graft infiltrating cells and alters the homeostasis of the lymphoid and myeloid compartment. Thus, IL-33 and its downstream effects need further evaluation as a possible therapeutic option for chronic allograft rejection.