There is an epidemic of immune-mediated disease in highly-developed industrialized countries. Such diseases, like inflammatory bowel disease, multiple sclerosis and asthma increase in prevalence as populations adopt modern hygienic practices. These practices prevent exposure to parasitic worms (helminths). Epidemiologic studies suggest that people who carry helminths have less immune-mediated disease. Mice colonized with helminths are protected from disease in models ofcolitis, encephalitis, Type 1 diabetes and asthma. Clinical trials show that exposure to helminths reduce disease activity in patients with ulcerative colitis or Crohn's disease. This chapter reviews some of the work showing that colonization with helminths alters immune responses, against dysregulared inflammation. These helminth-host immune interactions have potentially important implications for the treatment of immune-mediated disea ses.
Epidemiology ofImmune-Mediated Disease and WormsPathogens and parasites have evolved mechanisms to modulate or evade host immune responses. These adaptations permit survival of the invading organism. Our work extends this concept. We hypothesized that our immune systems are adapted "to expect" confrontations with other organisms and that loss of these confrontations permits immune dysfunction that can cause disease.' People living in highly-developed industrialized countries enjoy increasingly hygienic environments, which restricts exposure to infectious agents including helminths. We have focused on loss ofhelminth exposure as the major environmental change permitting the current epidemic of immune mediated disease.It is apparent that environmental change underlies the increasing prevalence of immune-mediated disease. Highly regulated immune responses protect us from pathogens and malignancy. However, when dysregulated or mis-targered, these immune responses produce inflammatory disease. Over the last 70 years, immune-mediated diseases like inflammatory bowel disease (IBD), multiple sclerosis (MS), Type 1 (autoimrnune) diabetes (TID) and asthma have become common in industrialized highly developed countries but remain rare in less-developed countries. Patients with IBD have chronic inflammation of the small and/or large intestine that results in bleeding, ulceration, strictures and perforation. IBD was uncommon prior to the 1940s, but now affiicts more than 3 million people in the United States and Europe.' As countries develop economically, IBD in the population increases.P Patients with MS have immune-mediated inflammatory destruction of the central nervous system. MS shares the same geographical and temporal distribution with IBD 4 and as countries develop improved san itation, the prevalence ofMS increases.' Patients with Tl D have immune-mediated destruction of pancreatic l3-ce11s that make insulin . Like MS and IBD,