Damage to the enteric nervous system in experimental colitis.

Inflammation of the intestine causes pain and altered motility, at least in part through effects on the enteric nervous system. While these changes may be reversed with healing, permanent damage may contribute to inflammatory bowel disease (IBD) and post-enteritis irritable bowel syndrome. Since little information exists, we induced colitis in male Sprague-Dawley rats with dinitrobenzene sulfonic acid and used immunocytochemistry to examine the number and distribution of enteric neurons at times up to 35 days later. Inflammation caused significant neuronal loss in the inflamed region by 24 hours, with only 49% of neurons remaining by days 4 to 6 and thereafter, when inflammation had subsided. Eosinophils were found within the myenteric plexus at only at the earliest time points, despite a general infiltration of neutrophils into the muscle wall. While the number of myenteric ganglia remained constant, there was significant decrease in the number of ganglia in the submucosal plexus. Despite reduced neuronal number and hyperplasia of smooth muscle, the density of axons among the smooth muscle cells remained unchanged during and after inflammation. Intracolonic application of the topical steroid budesonide caused a dose-dependent prevention of neuronal loss, suggesting that evaluation of anti-inflammatory therapy in inflammatory bowel disease should include quantitative assessment of neural components.

Interleukin-5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infections.

Enteric nematode infections are characterized by both peripheral and tissue eosinophilia. The cytokine interleukin (IL)-5 is considered a critical factor in the proliferation and recruitment of eosinophils, however, studies suggest it plays little role in host defence, at least during primary Trichinella spiralis infections. Less is known concerning its role in host defence or in the inflammatory response that develops against challenge infections with the same parasite. We examined these questions by infecting IL-5 deficient and wild-type mice, with T. spiralis parasites. Both strains expelled the primary infection by day 21. Forty days after the primary infection, we challenged the mice with a second T. spiralis infection and counted tissue eosinophils and worms in the intestine. While wild-type mice developed a large tissue eosinophilia, IL-5 deficient mice showed little increase in eosinophil numbers within the intestine. Throughout the challenge infection, significantly larger worm burdens were recovered from IL-5 deficient mice, and worm expulsion was also significantly slower (day 21) compared to wild-type mice (day 14). Thus, unlike in a primary infection, IL-5 is not only essential for the onset of intestinal eosinophilia, but also makes a significant contribution to enteric host defence during challenge T. spiralis infections.