Experimental postoperative ileus: is Th2 immune response involved?

Abstract

Rationale: Postoperative ileus (POI) is a frequent complication arising after gastrointestinal surgery but pathogenesis of POI is still not fully understood. While Th1 immune cells are implicated in POI, the involvement of Th2 cells has not yet been clarified. Given the impact of reactive oxygen species (ROS) in the regulation of Th1 and Th2 balance, we hypothesized that not only Th1 but also Th2 immune response can be involved in the development of experimental POI. Methods: The intestinal transit test was performed using carbon gum arabic. Electron microscopy was employed to assess tissue morphology and the presence of immune cells. Cytokines, IgE and ROS were measured. Immune cells from Peyer's patches were analyzed by Flow Cytometry and toluidine blue staining was used for detection of mast cells. Transcriptional factors were analyzed by Western blot. Results: POI is associated with an increase in both Th2 cytokines and Th2 cells. We have further demonstrated that POI induces a Th2-dependent activation of memory and non-memory B cells. This was accompanied by an increase in a number of mast cells in the colon of POI mice as well by an increased IgE and histamine plasma levels. We found that POI-induced accumulation of ROS was associated with an increased expression of the transcriptional factors HMBGI, NF-κB, and p38. This increased expression seemed to be associated with a Th2 response. Conclusion: Th2 immune response can be involved in the activation of mast cells in POI, which was associated with ROS mediated activation of NF-κB and p38 MAPK signaling pathway.

The Role of Inflammatory Mediators in the Development of Gastrointestinal Motility Disorders

“…There is some consensus that ileus is primarily mediated by a TH1-mediated immune response, although there is some evidence suggesting the TH2 cells may also contribute to ileus [28,91,92]. This fits in with the trend that TH1 cytokines generally decrease intestinal contractile responses while TH2 cytokines, such as IL-4 and IL-13, increase gastrointestinal motility.…”

Polydatin inhibits mitochondrial damage and mitochondrial ROS by promoting PINK1‐Parkin‐mediated mitophagy in allergic rhinitis

“…26 Excessive ROS can affect the immune balance of Th1/Th2. 27 It has been confirmed that oxidative stress and excessive ROS play a pathogenic role in allergic rhinitis. 28 The antioxidant strategies can mitigate the harmful effects of ROS on the body.…”

“…Many metabolic processes in the body can generate ROS, such as the Haber‐Weiss reaction, and the mitochondria are the main source of ROS 26 . Excessive ROS can affect the immune balance of Th1/Th2 27 . It has been confirmed that oxidative stress and excessive ROS play a pathogenic role in allergic rhinitis 28 .…”

Systemic Cytokine Expression in Diabetes Is Associated with Prolonged Gastrointestinal Transit Times and Cardinal Gastroparesis Symptoms

“…For instance, it is well-established that the development of ileus after abdominal surgery is influenced by mechanical activation of macrophages residing in the wall of the gastrointestinal tract causing the release of especially Th1 cytokines leading to impaired motility and inefficient propulsive motions [ 19 ]. On the other hand, Th2 cytokines are generally considered motility-inducing, but some discrepancies in reported findings are seen, and the specific effect of a given cytokine on motility may be disease- and patient-specific [ 18 , 20 ]. The exact mechanism by which cytokines affect gastrointestinal motility is poorly understood.…”