Der gastroinestinale field effect – eine chirurgisch getriggerte immunologische Reaktion?

Abstract

Introduction: Standardized intestinal manipulation (IM) as a model for intestinal trauma leads to a localized bowel wall inflammation and hypomotility subsequently spreading over the entire nonmanipulated gastrointestinal tract. This phenomenon was defined as gastrointestinal field effect (FE) and is the functional base of the perpetuating paralytic ileus. This study should elucidate the role of mesenteric lymph nodes, of migrating immune cells and their possible blockage by FTY-720. Material and Methods: T cells were isolated and analyzed from the muscularis layer of the small and large bowel and from the blood of C57Bl/6-mice (WT), of lymph node deficient mice and of FTY-720 treated mice 24 hours after IM and sham-operation and after intraoperatively CSFE-labeling of the small bowel muscularis. The FE was determined by measuring the gastrointestinal and colon transit time, in vitro contractility of muscularis strips and by measuring the mRNA levels of proinflammatory cytokines (IL-6, TNF-α, MIP-1α, IL-10) by Taqman®-PCR. T cell surface markers were analyzed by FACS-Calibur (II). Results: We observed a 3fold reduction of T cells in the small bowel and a 4 fold upregulation of T cells in the colon after IM. We found CSFE labeled T cells in the colon after IM combined with CSFE-labeling of the small bowel in WT mice, but not after sham-operation. We did not observe a relocation of CSFE-labeled T cells in FTY-720 treated mice and lymph node deficient mice after IM. T cell analysis was performed. The gastrointestinal and the colon transit time were significantly improved in lymph node deficient mice and FTY-720 treated mice. There was also a contractility comparable to sham-operated mice and a 100fold downregulation of proinflammtory cytokines within the colonic muscularis after IM in the modified mouse strains. Conclusion: The FE is mediated by the migration and relocation of T cell subsets. The blockage of T cell migration such as by FTY-720 abolishes the FE. Teh FE is based on immunological mechanisms. Therefore, the postoperative ileus is obviously immunologically mediated.