Immunotherapy refers to therapy that is given to induce, improve or suppress the immune system as a way of treating disease.
One experimental form of immunotherapy is the treatment of autoimmune disease using helminths (parasitic worms) such as hookworms, threadworms or whipworms. These worms have evolved to live inside a host organism, on which they depend for nutrients. Helminthic infection has become thought of as a potential explanation for why the incidence of autoimmune diseases and allergy is lower in underdeveloped countries, yet increasing in industrialized countries.
In 2007, an expert in parasite immunology called P’ng Loke met with a 35 year old man who had deliberately swallowed parasitic worms in an attempt to treat his ulcerative colitis. The men began a research project which was published in the journal Science Translational Medicine in 2010.
Although the man who met Loke was in good health at the time, he had been suffering from intense symptoms of colitis only a few years earlier, including vomiting, diarrhea, abdominal pain, weight loss and rectal bleeding. In an attempt to discover a cure, the man had read the work of a gastroenterologist, immunologist and parasitologist Joel Weinstock who had performed pioneering research on the subject of helminthic therapy and treated autoimmune disease by infecting patients with whipworm and hookworm.
The results of Loke’s new case study suggested that helminths may relieve the symptoms seen in autoimmune disease by increasing mucus production. Loke examined the man’s medical records from before 2007 and then monitored his health from 2007 onwards. In 2004, the man had swallowed 500 whipworm eggs which he followed with another 1,000 eggs three months later. The eggs hatched and matured inside his gastrointestinal tract, where they would have “hooked” their heads into the intestinal lining. By the middle of 2005, almost all of the man’s symptoms had resolved and he no longer required drugs for his condition, aside from an occasional anti-inflammatory medication to control flare-ups. In 2008, the number of eggs in the man’s stool began to fall, but as the eggs disappeared, the colitis symptoms returned. The man therefore swallowed another 2,000 worms and found that his symptoms had almost vanished again a few months later. Colonoscopies were performed, which showed that wherever the worms had settled in his colon, the signs of colitis were either absent or significantly reduced.
During the symptom relapse in 2008, the researchers discovered that areas of tissue with active colitis had immune cells that were producing large amounts of the cytokine interleukin 17 (IL-17), but very low amounts of IL-22, a cytokine that has been associated with wound healing and mucus production. Once the worms were reintroduced to the colon however, there was a significant increase in the production of IL-22. Further analysis showed that areas of tissue where the helminths thrived had an increased level of carbohydrate metabolism, which is required for mucus production. Loke suggested it was possible that the mucus provides a defensive barrier between the gut and bacteria that stops the bacteria from triggering inflammation and moving into other tissues. As autoimmune disease is an overreaction of the immune system to harmless or even beneficial substances in the body, experts suspect that inflammation of the colon lining (colitis) occurs as a reaction against bacteria in the gut. Loke believes that when helminths are detected, the body boosts mucus production to defend against the worms and that this excess mucus may also calm an overactive immune system.
A number of rodent studies have shown helminth infestation to protect the animals against asthma, rheumatoid arthritis, colitis, type 1 diabetes and food allergies. A few human studies have also been conducted, the results of which have been promising.
In a 2005 study, published in the journal Gastroenterology, Weinstock and colleagues gave 52 colitis patients 2,500 whipworm eggs or a placebo once a fortnight for three months. The team found that symptoms improved in 13 (45%) of those who received the eggs, compared with only 4 (17%) of those who received a placebo.
Some researchers now believe that the incidence of conditions such as Chron’s disease are on the rise because today’s children are no longer exposed to infectious pathogens as they were in previous generations and that helminthic therapy is now needed to restore a natural autoimmune balance.