gms | German Medical Science

Introduction: Abdominal surgery results in a posttraumatic response of the intestine leading to postoperative ileus (POI). Several causes of POI have been identified, including the activation of inhibitory neural pathways on the one hand and a local inflammation within the intestinal muscularis on the other hand. Recently, interactions between the vagus nerve and the intestinal immune system have been described, demonstrating an antiinflammatory action of the vagus nerve in the late phase of POI. The aim of this study was to investigate the immunological influence of the vagus nerve in the early phase of POI.

Materials and methods: In a standard murine model of intestinal manipulation (IM) we investigated the effect of abdominal vagotomy (VGX), application of capsaicin (125 mg/kg KG s.c.), a potent inhibitor of vagal afferents compared to controls on the development of POI. 1h and 3h after IM we measured gene expression of IL-1β, IL-6, IL-10 and MIP-1α within the intestinal muscularis and mast cell activation in the peritoneal cavity using a beta-hexosaminidase assay. 24h after IM leukocyte infiltration into the muscularis externa was investigated by Hanker-Yates staining. Functional measurements included gastrointestinal and colonic transits.

Results: IL-1β-, IL-6-, IL-10-, MIP-1α-gene expression and mast cell tryptase were significantly increased 1h after IM compared to controls with no statistical difference between VGX and sham-VGX. However, 3h after IM, cytokine levels were significantly decreased in vagotomized animals and capsaicin-pretreated groups. Leukocyte infiltration increased significantly 24h after IM in the intestinal muscularis in VGX-animals compared to sham-IM and sham-VGX. The functional measurements showed no difference between vagotomized and non-vagotomized animals.

Conclusion: Our data demonstrate for the first time that elimination of bidirectional vagus signaling by VGX reduces inflammatory gene expression in the early phase of POI. Furthermore, we show that pro-inflammatory vagal stimuli are mediated via afferent nerve fibers. At the cellular level the vagus nerve inverts to an antiinflammatory function. Further experiments must identify the molecular switches of this Janus-faced vagal function.