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Impact of interleukin-12, oxidative burst, and iNOS on the survival of murine fecal peritonitis

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Abdominal sepsis due to secondary fecal peritonitis following anastomosis insufficiency is a rare but life threatening complication of colorectal surgery. The induction of IFN-γ by IL-12 is believed to play a key role in sepsis as it promotes antibacterial effector mechanisms such as oxidative burst or nitric oxide induction. The impact of gene deficiency for IL-12 (IL-12p40 KO), oxidative burst (p47phox KO), or NO induction (iNOS KO) on the outcome of fecal peritonitis was characterized using the murine Colon Ascendens Stent Peritonitis model (CASP). In the IL-12p40 KO model, 3 and 12 h after surgery, serum cytokine levels of IL-1β, TNF, IL-18, and IL-10 were analyzed. Expression of IL-1β, IL-10, IP-10, and MIP-1α was measured in lung and liver by RNAse Protection Assay. IL-12p40 and iNOS-deficient mice exhibited a significantly higher susceptibility to CASP as compared to the controls, whereas no significant difference was observed in p47phox KO mice. Absence of IL-12 resulted in delayed expression of proinflammatory cytokines and chemokines in both the liver and the lung, and was associated with significant reduction of IL-1β levels in the serum 12 h after CASP. IL-12 and iNOS possess protective functions in fecal murine peritonitis. Surprisingly, no significant contribution of oxidative burst to the immune response was observed. Overall, these findings suggest that IL-12 deficiency causes a profound delay of the immune response after polymicrobial challenge resulting in significantly increased susceptibility in the CASP model.

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Abbreviations

CASP:

Colon ascendens stent peritonitis

RPA:

RNAse protection assay

KO:

Knock-out

WT:

Wildtype

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Acknowledgements

We thank Antje Müller and Tanja Rossmann-Bloeck for expert technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft DFG (Graduiertenkolleg 840 “Host–pathogen interactions in generalized bacterial infections”, project B2 and B3; Klinische Forschergruppe Si208/5-1 “Immunosuppression und postoperative Sepsis”) and by the German Federal Ministry for Education and Research (NBL3 program, reference 01 ZZ 0103).

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Authors and Affiliations

  1. Chirurgische Klinik und Poliklinik, Technischen Universität München, Munich, Germany

    Markus Entleutner & Bernhard Holzmann

  2. Klinik und Poliklinik für Chirurgie, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich-Löfflerstr. 23b, 17487, Greifswald, Germany

    Tobias Traeger, Alexandra Westerholt, Albrecht Stier, Stefan Maier & Claus-Dieter Heidecke

  3. Institut für Med. Mikrobiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

    Klaus Pfeffer

Authors
  1. Markus Entleutner
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  2. Tobias Traeger
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  3. Alexandra Westerholt
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  4. Bernhard Holzmann
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  5. Albrecht Stier
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  6. Klaus Pfeffer
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  7. Stefan Maier
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  8. Claus-Dieter Heidecke
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Correspondence to Stefan Maier.

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Markus Entleutner, Tobias Traeger, Stefan Maier, and Claus-Dieter Heidecke contributed equally to the work.

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Entleutner, M., Traeger, T., Westerholt, A. et al. Impact of interleukin-12, oxidative burst, and iNOS on the survival of murine fecal peritonitis. Int J Colorectal Dis 21, 64–70 (2006). https://doi.org/10.1007/s00384-004-0707-0

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  • DOI: https://doi.org/10.1007/s00384-004-0707-0

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