International Journal of Colorectal Disease

, Volume 21, Issue 8, pp 747–753

Rapamycin decreases leukocyte migration in vivo and effectively reduces experimentally induced chronic colitis

Authors

    • Department of SurgeryUniversity of Regensburg
  • Matthias Hornung
    • Department of SurgeryUniversity of Regensburg
  • Christine Sattler
    • Department of SurgeryUniversity of Regensburg
  • Markus Guba
    • Department of SurgeryUniversity of Regensburg
    • Department of SurgeryLudwig-Maximilians-University
  • Markus Steinbauer
    • Department of SurgeryUniversity of Regensburg
  • Matthias Anthuber
    • Department of SurgeryUniversity of Regensburg
  • Hans Herfarth
    • Department of Internal Medicine IUniversity of Regensburg
  • Hans J. Schlitt
    • Department of SurgeryUniversity of Regensburg
  • Edward K. Geissler
    • Department of SurgeryUniversity of Regensburg
Original Article

DOI: 10.1007/s00384-005-0793-7

Cite this article as:
Farkas, S., Hornung, M., Sattler, C. et al. Int J Colorectal Dis (2006) 21: 747. doi:10.1007/s00384-005-0793-7

Abstract

Background

Immunosuppressive calcineurin inhibitors, like cyclosporine (CsA), can be used for the clinical management of severe ulcerative colitis. However, patients treated with CsA are at a risk for developing kidney failure and may be more susceptible to colon cancer. Furthermore, severe neurotoxicity and hypertension are common problems. To avoid the side effects of CsA, new immunosuppressive drugs to treat colitis are needed. The aim of the present study was to test the immunosuppressive mammalian target of rapamycin inhibitor rapamycin in an experimental model of chronic colitis and to compare its effectiveness with CsA.

Methods

Chronic colitis was established in Balb/c mice after four feeding cycles of dextran sodium sulfate. Because leukocyte recruitment to sites of intestinal inflammation is crucial for the development of chronic colitis, intravital microscopy was used to study the effect of rapamycin and CsA on leukocyte–endothelium interactions and leukocyte extravasation. To assess the degree of colitis, histological sections were evaluated.

Results

Both rapamycin and cyclosporine effectively reduced leukocyte sticking (>60%) in submucosal venules, as compared to controls. Furthermore, rapamycin, but not CsA, reduced (>35%) leukocyte extravasation in the mucosa. Both rapamycin and CsA treatments significantly improved the histologic inflammation score.

Conclusion

Our in vivo results demonstrate that rapamycin reduces leukocyte sticking and extravasation during chronic colitis induction and proves to be as effective as CsA at reducing experimental chronic colitis. These results support the use of rapamycin in clinical trials to avoid serious side effects of CsA therapy in chronic colitis patients.

Keywords

RapamycinCyclosporineExperimental chronic colitisIn vivo microscopy

Abbreviations

CsA

Cyclosporine

DSS

Dextran sodium sulfate

Copyright information

© Springer-Verlag 2005