Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 21, 2003
Publication Date: March 1, 2003
Citation: Elliott, D.E., Crawford, C., Li, J., Blum, A., Metwali, A., Qadir, K., Urban Jr, J.F., Weinstock, J.V. 2003. Exposure to schistosome eggs protects mice from tnbs colitis. American Journal of Physiology - Gastrointestinal and Liver Physiology. 284:6385-6391 (2003)
Interpretive Summary: Inflammatory bowel disease (IBD) probably results from failure to down-regulate a chronic immune-activated inflammatory process in the intestine. IBD is rare in underdeveloped countries with poor sanitation where worm infections are common, but common in industrialized countries were public health measures preclude worm infections of humans. The development of worms in the intestine stimulates a potent type of immune response that restricts the inflammatory response that often accompanies destruction of intestinal tissue. The logical conclusion from this circumstantial information is that moderate levels of infection with worm parasites may be beneficial in limiting the extent of inflammation that results in chronic disease. There have been evolutionary pressures to develop an immune system that can control both intracellular infections, like certain bacteria and viruses, and extracellular infections with worms. .Elimination of exposure to worms could result in an imbalance in the protective and modulating affects of immunity. This hypothesis was tested by chemically induction of intestinal inflammation in mice followed by infection with a worm parasite to stimulate an appropriate immune response. The results indicated that immunity to the parasite reduced the level of induced intestinal inflammation. These results will provide an important theoretical basis for examining the role of parasite infections in both humans and livestock that exhibit unrestricted intestinal inflammation that leads to disease.
Crohn's disease appears to result from dysregulated Th1-type mucosal inflammation probably targeted to intestinal lumenal contents. Crohn's disease is rare in tropical third world countries but prevalent in developed countries with temperate climates. Crohn's disease was rare before the 1930's but had a rapid rise in incidence after 1940. Other autoimmune diseases also share this geographic and temporal distribution. In contrast, exposure to helminthic parasites is common in tropical third world countries but is increasingly rare in developed countries. Helminthic parasites induce strong Th2 responses in the host. We hypothesize that strong Th2 response due to helminths may attenuate development of the excessive Th1 response that characterizes Crohn's' disease. We tested this hypothesis in mice with murine schistosomiasis and dthe TNBS model of intestinal inflammation. Mice previously exposed to schistosome eggs had diminished IFNgamma secretion from anti-CD3-stimulated spleen and MLN cells and protected mice from developing lethal inflammatory colitis. The eradication of helminthic parasites may explain the unique epidemiology of Crohn's disease and other autoimmune illness.