The role of lymphoid tissue in the attenuation of the postoperative ileus

Abstract

Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune-mediated. The aim of this study was to investigate the role of secondary lymphoid organs [mesenteric lymph nodes (MLN), gut-associated lymphoid tissue (GALT)] in IM-mediated FE by employing mice with deficient secondary lymphoid organs (aly/aly, MLN ex) or by administration of 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol (FTY720), an immunomodulating agent that inhibits emigration of lymphocytes out of lymphoid organs. Small bowel muscularis, and colonic muscularis from wild-type mice as control, from aly/aly mice, FTY720-treated mice (daily dose of 1.0 mg/kg mouse ip starting 3 days before surgical procedure), and wild-type mice that had undergone removal of mesenteric lymph nodes before IM (MLN ex mice) were obtained after selective IM of the jejunum or sham operation. FE was analyzed by measuring transit time of orally administered fluorescent dextran in the gastrointestinal tract [geometric center (GC) of fluorescent dextran], colonic transit time, infiltration of myeloperoxidase-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α] were determined by Taqman-PCR. We observed a significantly reduced upregulation of proinflammatory cytokines (IL-6, TNF-α, MIP-1α) in colonic muscularis of MLN ex mice, aly/aly mice, and FTY720-treated mice compared with wild-type mice. Contractility of circular muscularis strips of the colon but not the jejunum was significantly improved in aly/aly mice and FTY720-treated wild-type mice. Additionally, inflammation of the colon determined by the number of myeloperoxidase-positive cells and colonic transit time were significantly improved in aly/aly mice, FTY720-treated wild-type mice, and in MLN ex mice. In summary, lack of secondary lymphoid organs (MLN + GALT) in aly/aly mice or administration of FTY720 abrogated FE after IM as opposed to wild-type mice. These data demonstrate that secondary lymphoid organs are involved in the propagation of FE and postoperative ileus. FTY720 indirectly affects FE by inhibiting migration of activated T cells from the jejunum and adjacent secondary lymphoid organs to the colon. These findings support the crucial role of the adaptive immune system in FE, most likely by a sphyngosine 1-phosphate-dependent mechanism.

Electroacupuncture for the prevention of postoperative gastrointestinal dysfunction in participants undergoing vascular laparotomy under general anesthesia: a randomized controlled trial

“…Acupuncture treatments are complex, multicomponent interventions. In sham-controlled trials that attempt to control only certain potentially therapeutic acupuncture-specific components, such as location, insertion depth, stimulation, needle size, and number [35], the moderately large nonspecific effects of sham acupuncture can decrease the reliability and the usefulness of the test results [36]. …”

Post‐operative ileus: definitions, mechanisms and controversies

“…An inflammatory response is thought to follow this early neural phase and has been linked to the sustained period of gut dysfunction seen in PPOI. Tissue damage from intestinal handling activates resident muscularis macrophages and peritoneal mast cells via the release of damage‐associated molecular patterns, resulting in local cytokine release, an inflammatory infiltrate of monocytes and neutrophils, gut wall oedema and impaired intestinal smooth muscle function 2,41,56,57 . Degree of peritoneal breach has been correlated with the release of inflammatory mediators 58 ; increasing wound length and open surgery are clinical risk factors for PPOI 8 .…”

“…Tissue damage from intestinal handling activates resident muscularis macrophages and peritoneal mast cells via the release of damage-associated molecular patterns, resulting in local cytokine release, an inflammatory infiltrate of monocytes and neutrophils, gut wall oedema and impaired intestinal smooth muscle function. 2,41,56,57 Degree of peritoneal breach has been correlated with the release of inflammatory mediators 58 ; increasing wound length and open surgery are clinical risk factors for PPOI. 8 In murine models, this inflammatory phase begins 3-4 h after surgery, peaks at 24 h post-operatively and correlates with the degree of intestinal handing.…”

Therapie postoperativer Darmpassagestörungen in der Intensivmedizin

“…IL12 bindet an T1-Helferzellen, die auch in nicht affektierte Regionen des Abdomens wandern und dort per Sekretion von TNF-α und die darüber gesteuerte Aktivierung von Makrophagen eine vom eigentlichen Ort der Intervention entfernte Entzündungsreaktion auslösen. Dieser Effekt erklärt auch die Wirkung von liegenden Drainagen, die eine lokale Entzündungsreaktion auslösen, auf das verzögerte Wiedereinsetzen der Darmpassage [10,11].…”