Effect of Schistosoma mansoni-induced granulomatous inflammation on murine gastrointestinal motility.

In Schistosoma mansoni-infected mice, gastrointestinal transit was measured in vivo and the neuromuscular function of longitudinal muscle strips of inflamed ileum and noninflamed gastric fundus was assessed in vitro. Eight weeks after infection, the ileal wall was acutely inflamed, as shown by a mucosal inflammatory infiltrate, leading to an increase in mucosal thickness, in myeloperoxidase (MPO) activity, and in interleukin (IL)-1beta production. At that time, both gastrointestinal transit and in vitro ileal contractility were normal. Twelve weeks after infection, chronic granulomatous inflammation led to proliferation of the muscle layer and to a further increase in MPO activity, whereas IL-1beta production normalized. Gastrointestinal transit was decreased, whereas in vitro ileal contractility was increased irrespective of the contractile stimulus. In vitro incubation with IL-1beta (10 ng/ml for 60 min) significantly increased ileal contractility only at 8 wk after infection. Indomethacin, tetrodotoxin, and atropine had no differential effect on ileal contractility in controls and infected mice. In vitro contractility of noninflamed gastric fundus was normal both 8 and 12 wk after infection. We conclude that intestinal schistosomiasis 8 wk after infection is associated only with structural changes of the ileum, whereas 12 wk after infection, both structural and functional changes are present. These changes are characterized by increased ileal wall thickness, decreased gastrointestinal transit, and increased smooth muscle contractility restricted to the inflamed gut segment.

Schistosoma mansoni infection causing diffuse enteric inflammation and damage of the enteric nervous system in the mouse small intestine.

Schistosomiasis mansoni is a major health problem, mainly occurring in developing countries. A large proportion of infected individuals suffers from motility-related gastrointestinal problems. In the present study, the diffuse inflammatory response in the small bowel wall, as compared to the egg-induced granulomatous inflammation, was investigated. For this purpose, OF1 mice infected with Schistosoma mansoni 8-16 weeks prior to the experiment, and uninfected control mice were studied. The ileum showed both a diffuse mucosal inflammation as well as a granulomatous reaction. The diffuse mucosal inflammation caused an increase in the thickness of the mucosa, with blunting of the villi. A significant, transient increase of thickness of the muscularis propria after 12 weeks of infection was noted. There was an infection-related mast cell infiltrate in the muscularis propria, consisting of formalin fixation-insensitive connective tissue mast cells. Ganglionitis of the myenteric plexus was noted. Rarely, ganglia of the myenteric plexus contained apoptotic cells. A general pharmacological set of experiments showed a significant increase in intestinal contractility, both to exogenously administered, as well as to endogenously released neurotransmitters. Our results demonstrate that S. mansoni infection in the mouse ileum leads to diffuse specific enteric inflammation that is associated with an enhanced response to contractile agents.