Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hookworms, whipworms, and threadworms that have evolved to live within a host organism on which they rely for nutrients. The theory behind helminth therapy is that these worms reduce negative immune responses due to their TH2 immune response that downregulates the abnormal T-cell responses recently associated with autoimmune disorders. This therapy ties to the hygiene hypothesis in that the lack of exposure to bacteria and parasites such as helminths can cause a overactive immune system leading to being more susceptible to autoimmune disease. Helminth worms are members of two phyla: nematodes, which are primarily used in human helminthic therapy, and flat worms (trematodes). Helminthic therapy consists primarily of the inoculation of the patient with specific parasitic intestinal nematodes (or other helminths). A number of such organisms are currently being investigated for their use as treatment, including: Trichuris suis ova, commonly known as pig whipworm eggs; Necator americanus, commonly known as hookworms; Trichuris trichiura ova, commonly referred to as human whipworm eggs; and Hymenolepis diminuta, commonly known as rat tapeworm. While the latter four species may be considered to be mutualists – providing benefit to their host without causing long term harm – there are other helminth species that have demonstrated therapeutic uses, but these have a potential to cause harmful side effects, and therefore do not share the ideal characteristics for a therapeutic helminth. These include Ascaris lumbricoides, commonly known as human giant roundworm; Strongyloides stercoralis, commonly known as human roundworm; Enterobius vermicularis, commonly known as pinworm or threadworm; and Hymenolepis nana, also known as dwarf tapeworm. Current research targets Crohn's disease, ulcerative colitis, inflammatory bowel disease, coeliac disease, multiple sclerosis and asthma. Helminth infection has emerged as one possible explanation for the low incidence of autoimmune diseases and allergies in less developed countries, while reduced infection rates have been linked with the significant and sustained increase in autoimmune diseases seen in industrialized countries.
Incidence of autoimmune diseases and parasitic infestation While it is recognized that there is probably a genetic disposition in certain individuals for the development of autoimmune diseases, the rate of increase in incidence of autoimmune diseases is not a result of genetic changes in humans; the increased rate of autoimmune-related diseases in the industrialized world is occurring in too short a time to be explained in this way. There is evidence that one of the primary reasons for the increase in autoimmune diseases in industrialized nations is the significant change in environmental factors over the last century. It is posited that the absence of exposure to certain parasites, bacteria, and viruses is playing a significant role in the development of autoimmune diseases in the more sanitized and industrialized Western nations. Lack of exposure to naturally occurring pathogens and parasites may result in an increased incidence of autoimmune diseases. Correlational data has shown the prevalence of helminthic infections to be greatest south of the equator where the rates of autoimmune diseases such as multiple sclerosis are low. This is consistent with the hygiene hypothesis which suggests that helminthic infections protect individuals from developing auto-immune diseases rather than being an agent responsible for inducing them. A complete explanation of how environmental factors play a role in autoimmune diseases has still not been proposed. Epidemiological studies such as the meta-analysis by Leonardi-Bee et al., however, have helped to establish the link between parasitic infestation and their protective role in autoimmune disease development.
Hypotheses Although the mechanisms of autoimmune disease development are not fully understood, there is broad agreement that the majority of autoimmune diseases are caused by inappropriate immunological responses to innocuous antigens; these are generally called the hygiene hypothesis, but exist in several variants. One version proposes that the dysfunction is driven by a branch of the immune system known as the T helper cells (Th or TH). Two other refinements to the hygiene hypothesis exist: The "old friends" hypothesis, and the "microbiome depletion" hypothesis.
TH1 vs. TH2 response regulation Extra-cellular antigens primarily trigger the TH2 response, as observed with allergies, while intracellular antigens trigger a TH1 response. Th cells can be divided into subtypes based on the characteristic cytokines they secrete. TH2 immune responses result in the release of cytokines associated with inflammation reduction such as interleukin 4, interleukin 5, and interleukin 10. These cytokines are thought to reduce the symptoms of many autoimmune disorders. Conversely, TH1 immune responses are characterized by the cytokines interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα), both of which are thought to increase inflammation and worsen the progression of autoimmune diseases and their symptoms. The antagonism between these two types of immune response is a central theme of one proposal for the biological basis of the hygiene hypothesis, which suggests that there is a regulatory action between the two types of response. The observation that allergies and autoimmune response are increasing at a similar rate in industrialized nations appears to undermine this explanation of hygiene hypothesis.
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