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Title: EXPOSURE TO SCHISTOSOME EGGS PROTECTS MICE FROM TNBS COLITIS

Author
item ELLIOTT, DAVID - IOWA CITY, IOWA
item LI, JIE - IOWA CITY, IOWA
item BLUM, ARTHUR - IOWA CITY, IOWA
item MEETWALI, AHMED - IOWA CITY, IOWA
item QADIR, KHURRAM - IOWA CITY, IOWA
item Urban, Joseph
item WEINSTOCK, JOEL - IOWA CITY, IOWA

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2002
Publication Date: 6/13/2003
Citation: Elliott, D.E., Li, J., Blum, A., Meetwali, 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(3):6385-6391.

Interpretive Summary: Inflammatory bowel diseases (IBD) have been increasing in developed but not lesser developed countries over the last 50 years. Knowledge of the nature of IBD indicates that the inflammatory pattern is typical of a reaction that is normally ameliorated by the normal immune response to parasitic worms. There is a counter-regulatory balance between immune and inflammatory responses to intracellular bacteria and viruses versus responses to extracellular worm parasites. The fact that individuals from developed countries have good hygiene and are generally worm-free while those from lesser developed countries are not may account for demographic pattern of IBD worldwide. This proposition may also be relevant to the appearance of certain diseases in livestock, especially those kept parasite-free in confinement where the composition of infectious agents is altered from natural exposure conditions. Support for this hypothesis through experimentation in rodent models and observations of human patient will provide useful therapies to control intestinal pathologies in both humans and livestock.

Technical Abstract: Two polarized patterns (Th1 and Th2) of cytokine production regulate inflammatory responses. Each cytokine pattern inhibits production of the opposing pattern. Lymphocytes from inflamed intestine due to Crohn's diseases secrete a Th1 pattern of cytokine. Crohn's disease is most prevalent in highly industrialized countries with temperate climates. It occurs rarely in tropical third world countries with poor sanitation. We propose that under exposure to an infectious agent predispose individuals to Crohn's disease. Parasitic worms are common in tropical climates and in populations subject to crowding and poor sanitation. Children are most subject to infection. Many worm parasites develop in the human gut where the host mounts a mucosal Th2 inflammation that can limit the infection. These parasites are potent stimulators of mucosal Th2 responses that can also modulate immune responses to unrelated parasitic, bacterial and viral infections. In contrast, people in developed countries live in a relatively hygienic environment free from parasitic infection. Perhaps failure to acquire these parasites and to experience mucosal Th2 conditioning predisposes to the overactive Th1 inflammation that characterizes Crohn's disease.