The possible link between de-worming and the emergence of immunological disease

A major objective of our laboratory is the study of the various complex host immunological responses to helminths. Helminths are a group of worm-like organisms, some of which live in the intestinal lumen or host tissue. Helminths include pinworms (Enterobius vermicularis), whipworms (Trichuris trichiura), hookworms (ie, Ancylostoma duodenale), schistosomes (ie, Schistosoma mansoni), and tapeworms (ie, Diphyllobothrium, Taenia saginata, and Taenia solium). In response to helminths, the host develops a Th2-type inflammation that limits worm colonization and tissue injury. Being gastroenterologists, we are keenly interested in determining the cause of inflammatory bowel disease (IBD) (also known as Crohn’s disease and ulcerative colitis). IBDs are destructive, chronic inflammatory diseases of the intestine that are increasing in frequency in developed countries. Various demographic studies in defined geographical areas support the premise that the incidence of IBD is strongly influenced by environment and that the data are not simply a consequence of improvements in diagnosis. Our laboratory has examined questions related to immunoregulation on intestinal mucosal surfaces. This interest both in helminths and IBD has led to development of a new hypothesis suggesting that lack of helminthic exposure increases the risk for acquiring some immunological diseases. The effect of helminths on the host’s immune system is well-documented. This and other experimental data from both human and animal research now provide substantial support for this hypothesis. Exposure to most helminths carries little pathological potential because of our Th2 reaction. Stimulation of the immune system by various antigens triggers the release of host cytokines that orchestrate the immune response. The Th1 cytokine pattern, characterized by the secretion of interleukin-12 (IL12) and interferon (IFN ), is the usual response to bacterial or viral invasion. IFN strongly promotes macrophage activation and the production of complement forming antibodies. Th1-type inflammations are rich in activated macrophages and lymphocytes. The Th2 response is associated with interleukin-4 (IL4), interleukin-5 (IL5), and interleukin-13 (IL13) release, as well as immunoglobulin E (IgE) and eosinophilia. This limits helminthic colonization and is the pattern of inflammation most frequently associated with allergy. Along with others, we established that infestation with helminths, which induce Th2-type inflammation, down-modulates the Th1 immune response to unrelated parasitic, bacterial, and viral infections (Fig 1). People colonized with helminths mount less of a Th1 response or even a Th2 response to unrelated antigenic exposures. For instance, Ethiopians colonized with helminths have hyporesponsive T-cells and delayed-type skin hypersensitivity responses to recall antigens compared to worm-free, control populations. People acquire helminths through contact with soil, food, and water containing the infective forms of these organisms. Children, when playing, often come into contact with soil, and this, coupled with the practice of suboptimal hygiene, makes them highly susceptible to worm colonization (Fig. 2). Until the onset of modern day sanitation and a clean lifestyle, worm colonization was essentially universal. While this is still the case in less-developed countries, few people in industrial societies today harbor helminths. It occurred to us that perhaps the loss of helminths and their Th2 stimulus has had some negative medical consequences in technologically advanced countries. Crohn’s disease (CD) and multiple sclerosis are two From the Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, and The Immunology & Disease Resistance Laboratory, United States Department of Agriculture.