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Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus
  1. F O The1,
  2. R J Bennink2,
  3. W M Ankum3,
  4. M R Buist3,
  5. O R C Busch4,
  6. D J Gouma4,
  7. S van der Heide5,
  8. R M van den Wijngaard1,
  9. W J de Jonge1,
  10. G E Boeckxstaens1
  1. 1
    Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
  2. 2
    Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
  3. 3
    Department of Gynaecology and Obstetrics, Academic Medical Center, Amsterdam, The Netherlands
  4. 4
    Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
  5. 5
    Department of Allergy, University Medical Center, Groningen, The Netherlands
  1. G E Boeckxstaens, Department of Gastroenterology and Hepatology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; g.e.boeckxstaens{at}amc.uva.nl

Abstract

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from decreased mast cell activation and impaired intestinal inflammation.

Objective: To quantify mast cell activation and inflammation in patients undergoing conventional and minimal invasive surgery.

Methods: (1) Mast cell activation (ie, tryptase release) and pro-inflammatory mediator release were determined in peritoneal lavage fluid obtained at consecutive time points during open, laparoscopic and transvaginal gynaecological surgery. (2) Lymphocyte function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) mRNA as well as leucocyte influx were quantified in non-handled and handled jejunal muscle specimens collected during biliary reconstructive surgery. (3) Intestinal leucocyte influx was assessed by 99mTc-labelled leucocyte single photon emission computed tomography (SPECT) – computed tomography (CT) scanning before and after abdominal or vaginal hysterectomy.

Results: (1) Intestinal handling during abdominal hysterectomy resulted in an immediate release of tryptase followed by enhanced interleukin 6 (IL6) and IL8 levels. None of the mediators increased during minimal invasive surgery except for a slight increase in IL8 during laparoscopic surgery. (2) Jejunal ICAM-1 and iNOS mRNA transcription as well as leucocyte recruitment were increased after intestinal handling. (3) Leucocyte scanning 24 h after surgery revealed increased intestinal activity after abdominal but not after vaginal hysterectomy.

Conclusions: This study demonstrates that intestinal handling triggers mast cell activation and inflammation associated with prolonged postoperative ileus. These results may partly explain the faster recovery after minimal invasive surgery and encourage future clinical trials targeting mast cells to shorten postoperative ileus.

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Footnotes

  • Funding: Supported by the Technology Foundation STW, Applied Science Division of NWO, and the Technology Program of the Ministry of Economic Affairs (NWO-STW, grant AKG 5727 to F.O.T. and R.vd W.).

  • Competing interests: None.

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