Wickelgren's "Can worms tame the immune system?" 2004

From Biol557

• Subtitle: "Researchers are investigating the use of parasites as remedies for inflammatory bowl disease and other disorders of hyperimmunity."
• Some researchers believe that substances derived from parasitic worms may be useful in treating Inflammatory Bowel Disease (IBD) or other autoimmune disorders.
• Helminths are parasitic worms such as flukes, flatworms, tapeworms, and pinworms.
• It has been shown in mice that administration of extracts of helminths can reduce / prevent allergic reactions, reduce severity of an MS-like disorder, and block the development of type I diabetes.
• New data suggests that these factors take effect by invigorating the activities of T regulatory cells, which serve to slow or dampen the natural immune response.
• However, worm therapy is not yet ready for real use. We need to do more trials, replicate results, and figure out how all this is working.

[edit] Microbe medicine

• The hygiene hypothesis suggests that microbes are responsible for training our immune system and therefore, too much cleanliness can be a bad thing.
• A group in Venezuela was the first to show that helminths may provide immunological benefits.
  • They showed that children infected with helminths had fewer allergic reactions and that infected children with helminths treated with antihelminths had increased allergic reactions.
• So another researcher noticed that IBD occurred only in weathly populations in which there is almost no infection of helminths. Thus, he posited that administering the helminths might actually yield a protective effect against the body's own immune system.
• And now we're getting data suggesting that these helminths excite T regulatory cells, which dampen the immune response.
• Then we found that children in Africa (where asthma occurs because of allergic reactions to the common dust mite), children who were infected with a certain parasite were less allergic to the asthma-causing mite. They also found elevated IL10 levels in the infected children, which makes sense because IL10 is secreted by T regulatory cells.
• We used to think that Th1 and Th2 (both T helper cells) were antagonistic in how much the immune system reacted, but now we think that they both overreact because they aren't properly regulated by T regulatory cells (which, can be encouraged to inhibit with increased amounts of IL10).
• There is new evidence suggesting that it isn't just levels of cytokines changed by helminths, but also changes in the function of innate immune cells.

[edit] Diet of worms

• We got more experimental results showing that administration of worms or their eggs increased resistance to inflammation induction (a model of IBD).
• We even did two "larger" (but not very large) trials with administration of worm'ed drinks versus control drinks and found that those given worms showed resistance to their diseases (ulcerative colitis and Crohn disease).
  • "However, Lichtenstein warns that the Crohn’s disease trial lacked a placebo group and the colitis results fell short of remission, the usual endpoint for trials."
• Now they are working to develop a capsule form of worm administration for use in a large, double-blind study.

[edit] Sidebar: Wielding worms at asthma and autoimmunity

• People are getting pretty excited about worm therapy and are looking to apply it in three areas:
  • In allergies it has been shown that killing the helminth infections of children increased their risk of asthma.
  • In asthma, it has been shown that people with helminths have fewer asthma attacks and fewer eosinophils in their lungs (cells associated with asthma attacks).
  • In Diabetes and MS, it was shown that administration of worms could completely stop the onset of DT1 in mice (if administered early in life) and could increase hind limb movement and decrease the number of autoreactive T cells in the CNS of MS-like mice.
• Best line: "Aesthetically, it's a lot to swallow."