Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

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 nonhandled 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.

Effects of nerve growth factor antagonist K252a on peritoneal mast cell degranulation: implications for rat postoperative ileus

“…In line with previous studies, IM in our model resulted in a rapid degranulation of PMCs, as judged by the peritoneal increase of the CTMC-specific product RMCP-6 (3,7,23,26). Intestinal manipulation also resulted in a delay of the GI transit and produced inflammation of manipulated intestinal segments as previously reported (10,11).…”

“…A major event evoked by IM during abdominal surgery is the activation of peritoneal mast cells (PMCs), observed in mice and humans (2,3,7,23,26), suggesting a role of mast cells (MCs) in the pathogenesis of POI. In addition, mast cell-deficient knockout mice suffer from a less severe POI, and MC-stabilizing drugs such as ketotifen and doxantrazole prevent POI in mice (3).…”

Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

“…We employed a semi-quantitative scoring system to compare the degree of inflammation between the sham and POI groups. 15,19 Calprotectin and Tryptase Expression…”

Berberine Ameliorates Intestinal Mucosal Barrier Damage Induced by Peritoneal Air Exposure

“…[17][18][19] Therefore, methods to explore effective treatment for intestinal mucosal barrier damage are popular pursuits in modern surgery.…”