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Perioperative infliximab application has marginal effects on ischemia–reperfusion injury in experimental small bowel transplantation in rats

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Abstract

Purpose

Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia–reperfusion injury in isogenic transplantation.

Methods

Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five groups were defined: non-transplanted animals with no treatment (group 1), isogenic transplanted animals with vehicle treatment (groups 2/3) or with infliximab treatment (5 mg/kg body weight intravenously, directly after reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4) or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL staining, real-time RT-PCR, and contractility measurements in a standard organ bath were used for determination of ischemia–reperfusion injury.

Results

All transplanted animals showed reduced smooth muscle function, while no significant advantage of infliximab treatment was observed. Reduced infiltration of neutrophils was noted in the early phase in animals treated with infliximab. The structural integrity of the bowel and infiltration of ED1-positive monocytes and macrophages did not improve with infliximab treatment. At 3 h after reperfusion, mRNA expression of interleukin (IL)-6, TNF-α, IL-10, and iNOS and MCP-1 displayed increased activation in the infliximab group.

Conclusion

The protective effects of infliximab in the early phase after experimental small bowel transplantation seem to be unrelated to ischemia–reperfusion injury. The promising effects in allogenic transplantation indicate the need for further experiments with infliximab as complementary treatment under standard immunosuppressive therapy. Further experiments should focus on additional infliximab treatment in the setting of acute rejection.

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Conflicts of interest

None.

Funding sources

This study was supported by grants from Deutsche Forschungsgemeinschaft (KFO 115/1-1, Teilprojekt 3) and the BONFOR Program of the University of Bonn (O-112.0024, O-112.0013 and O-112.0015).

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Authors and Affiliations

  1. Department of Surgery, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany

    T. Pech, J. Fujishiro, T. Finger, M. Praktiknjo, M. von Websky, S. Wehner, J. C. Kalff & N. Schaefer

  2. Department of Pediatric Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan

    J. Fujishiro

  3. Department of Pediatric Surgery, University of Tsukuba, Tsukuba, Japan

    J. Fujishiro

  4. Department of Hepatobiliary Pancreatic Surgery, Mie University Graduate School of Medicine, Mie, Japan

    I. Ohsawa

  5. Division of Intestinal Transplantation, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, USA

    K. Abu-Elmagd

  6. Department of Surgery, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    N. Schaefer

Authors
  1. T. Pech
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  2. J. Fujishiro
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  3. T. Finger
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  4. I. Ohsawa
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  5. M. Praktiknjo
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  6. M. von Websky
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  7. S. Wehner
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  8. K. Abu-Elmagd
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  9. J. C. Kalff
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  10. N. Schaefer
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Corresponding author

Correspondence to N. Schaefer.

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Pech, T., Fujishiro, J., Finger, T. et al. Perioperative infliximab application has marginal effects on ischemia–reperfusion injury in experimental small bowel transplantation in rats. Langenbecks Arch Surg 397, 131–140 (2012). https://doi.org/10.1007/s00423-011-0853-0

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  • DOI: https://doi.org/10.1007/s00423-011-0853-0

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