Stress Causes Dyspepsia via Macrophage-mediated Duodenal Inflammation / 胃肠病学

ABSTRACT

Background: Epidemiological evidence revealed that stress is the causative factor of dyspeptic symptoms. It has been documented that duodenal inflammation is one of the key mechanisms of dyspepsia, and macrophage is crucial for inflammation. Aims: To determine whether patients with functional dyspepsia (FD) comorbid psychological stress have duodenal inflammation. Furthermore, to identify whether macrophage is involved in the mechanisms of stress-related duodenal inflammation by using water avoidance stress (WAS)animal model. Methods: Duodenal inflammation was observed and compared between FD patients with psychological factors and asymptomatic healthy controls. WAS mouse model with 1 h stress daily for 10 days was used to evaluate the duodenal inflammation at different time points to describe its dynamic changes. The role of macrophage in the development of duodenal inflammation was determined in an interventional study, in which the resident macrophages were depleted by clodronate liposomes. In both clinical and animal studies, the severity of duodenal inflammation was assessed by HE staining and immunocyte counts, the macrophage infiltration was detected by immunohistochemistry, and the expression of inflammatory cytokines was detected by real-time PCR. Results: FD patients with psychological factors developed severe duodenal inflammation in comparison with the healthy controls (immunocytes/HPF 138.91±7.13 vs. 81.44±23.60, P<0.000 1). At the same time, the expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-17A) were increased, while the expressions of anti-inflammatory cytokines (IL-10 and TGF-β) were decreased (all P<0.05). In WAS mouse model, a dynamic change in duodenal inflammation which peaked on day 5 was observed, and the changes of macrophage infiltrating in the duodenal tissue were consistent with the duodenal inflammation. Clodronate liposomes pretreatment could effectively deplete macrophages, protected the WAS mouse model against duodenal inflammation (immunocytes/HPF 75.10±4.08 vs. 202.43±5.18, P<0.001), with a marked reduction of the expressions of proinflammatory cytokines (IL-1β, TNF-α, and IL-8), and a marked elevation of the expression of anti-inflammatory cytokine IL-10 (all P<0.05). Conclusions: Psychological stress may lead to dyspeptic symptoms via macrophage-mediated duodenal inflammation.