Artikel
The Importance of Bacterial Translocation and Subsequent Signaling in the Etiology of Postoperative Ileus
Suche in Medline nach
Autoren
-
Burkhard Stoffels
- Uniklinikum Bonn, Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
-
Mariola Lysson
- Uniklinikum Bonn, Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
-
Jörg C. Kalff
- Uniklinikum Bonn, Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
-
Sven Wehner
- Uniklinikum Bonn, Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Bonn
| Veröffentlicht: | 20. Mai 2011 |
|---|
Gliederung
Text
Introduction: Inflammatory molecular and cellular events within the postsurgical intestinal muscularis cause postoperative ileus (POI). Translocating bacteria can lead to microbial invasion, escalation of immune defense and subsequently to conspicuous gastrointestinal dysfunction. Our goal was to determine if surgical manipulation provokes bacterial translocation and causes POI by triggering TLR-dependent signaling pathways.
Materials and methods: Wild type mice, TLR-2-/-, -4-/-, -9-/-, MyD88-/--, TRIF-/- and MyD88/TRIF-/--mice were subjected to intestinal manipulation (IM) to induce POI. In vivo motility was assessed by gastrointestinal transit (GIT), calculated as the geometric centre (GC) 24h after IM. Hanker Yates histochemistry on jejunal muscularis whole-mounts quantified neutrophil recruitment. Intestinal muscularis inflammatory mediator expressions were analyzed by quantitative PCR. IL-6 protein expression was detected by ELISA.
Results: IM caused a significant delay in the in vivo motility of wild-type mice (GC: CTL 9.3±0.3, BL6 IM 24h 3.4±0.5) while a singular, but above all the common lack of central adapter molecules MyD88 and TRIF GIT significantly improved (GC: MyD88/TRIF-/- IM 24h 6.7±2.2). Neutrophil recruitment was significantly reduced, especially in the double-knockout mice (cells/mm2: CTL 2±2, BL6 IM 24h 885±200, MyD88/TRIF-/- IM 24h 234±84). At mRNA level there was a significant reduction in the proinflammatory cytokines IL1-β (BL6 IM 24h 49.3±13.6-, MyD88/TRIF-/- IM 24h 2.3±1.2-fold) and IL6 (BL6 IM 24h 114.8±49.7-, MyD88/TRIF-/- IM 24h 5.3±1.8-fold) 3h after IM. This effect was also confirmed by protein expression analysis of the prototypical cytokine IL-6.
Conclusion: Our results show that lack of individual TLRs did not influence POI functionally following IM. The singular, but above all the simultaneous loss of downstream TLR, central adapter molecules (MyD88, TRIF) results in a significant improvement of postoperative inflammation and dysfunction. In summary, this study shows an essential role of TLR-mediated signaling by bacterial translocation in the etiology of POI.
