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<<   作成日時 : 2010/12/05 10:15   >>

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 ブタの鞭虫の卵を摂取し、寄生虫を使って潰瘍性大腸炎を治療しようとする試みにより、34才の患者は腹痛と血性下痢が劇的に改善した。2回目のブースターの虫卵の服用後4年間寛解状態にあるという。
 ブタ鞭虫を使った治療は2005年に最初に行われ、大腸炎ワクチンとして開発されている。
 寄生虫は免疫反応の特定のタイプを刺激することで効果をあらわす。粘液の生産を促し腸炎による潰瘍と炎症から腸の内層を保護する。
 最近5年で、クローン病や炎症性腸疾患、脳脊髄をおかす多発性硬化症などの自己免疫性疾患がこうした寄生虫感染で改善できる可能性が示されてきた。Th2型の免疫反応を賦活することで非特異的包括的なTh1型免疫反応を抑える抗炎症作用をもつ形になるという。
 寄生虫は腸内で微少出血を起こす可能性がありアレルギー反応も誘発しているため、10年以上先に何が起こるかを予測するのは不可能である。興味深いが一般的には推奨しかねると医師たちは言う。
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寄生虫によるアレルギー治療(2)
http://kurie.at.webry.info/200907/article_33.html
寄生虫によるアレルギー治療
http://kurie.at.webry.info/200807/article_4.html
多発性硬化症の寄生虫卵カクテル療法
http://kurie.at.webry.info/200803/article_29.html
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Man Doses Himself With a Parasite for Intestinal Problems
Doctors Investigate Worms as Possible Colitis Cure
http://abcnews.go.com/Health/WellnessNews/worm-cocktail-treat-intestinal-problems/story?id=12286308

By COURTNEY HUTCHISON, ABC News Medical Unit
Dec. 2, 2010

Catching an intestinal parasite is not usually considered desirable, but for a California man with severe gastrointestinal problems, dosing himself with worms was the answer to his prayers.

After reading preliminary research that suggested a whipworm found in pigs could help those with ulcerative colitis, the 34-year-old patient tracked down and ingested eggs from Trichuris trichiura, a similar roundworm that infects humans, in hopes of easing his own colitis.

After a few months, the abdominal pain and bloody diarrhea associated with the patient's ulcerative colitis improved dramatically, and after a second "booster" dose of worm eggs, he remains in remission more than four years later.

In hopes of better understanding how certain parasitic worms can be used to heal, doctors at New York University Langone Medical Center ran extensive testing on this man, the results of which were published Wednesday in Science Translational Medicine.

"Essentially this patient has been in remission for several years, with no other medication. For this individual, the goal is to remain infected for the rest of his life, but it's hard to know if that's a viable strategy for everyone. We don't have a good understanding of the risk," said P'ng Loke, assistant professor of medical parasitology at NYU Langone Medical Center and lead author of the study.

Treating colitis with worms is not new. The first human trials using pig whipworm took place in 2005. and this worm is being developed as a possible colitis vaccine, said Dr. Joel Weinstock, who pioneered this research while at the University of Iowa Carver College of Medicine. But Loke's case study may shed more light on how these worms protect and heal the colon.

Researchers found that the parasite works by inciting a specific type of immune response. In an attempt to rid the body of the worms, the immune system signals the body to produce more mucus, which in turn protects the lining of the gut from the ulcers and inflammation caused by the colitis.

Wonder Worms

Colitis isn't the only condition these little worms could possibly treat. In the past five years, research has suggested that other autoimmune disorders, such as Crohn's disease, an inflammatory bowel disease, and multiple sclerosis, which affects the brain and spinal cord, may also benefit from a targeted parasitic infection.

For Crohn's, MS and colitis, an overactive immune response results in excessive inflammation in the body. There are multiple ways that the immune system can fight off perceived threats, but with these disorders, the body sends out a nonspecific inflammation response that can ultimately harm the body's tissues. This blanket immune response is known as the Th1 pattern.

Becoming infected with whipworms, however, incites a very different immune response, known as Th2, said Dr. Gerard Mullin, director of Integrative Nutrition Services at the Johns Hopkins Hospital. "It's like a yin yang. The Th2 response is anti-inflammatory in nature, and it counteracts the Th1 response," he said.

Loke's study also suggests that the specific immune cells that are stimulated by the body's reaction to whipworms are particularly helpful because they regulate the amount of mucus in the gut.

"People with colitis have a deregulated immune response against the bacteria in the gut, and if you don't have a good mucous layer separating that bacteria from the gut wall, you're going to get the inflammatory response," which causes colitis. "The worms, by inducing the body to make more mucus, might be helping the ulcerative colitis," Loke said.

Worms -- the Natural Cure?

In nature, whipworm infections usually spread areas with poor sanitation, when fecal matter gets back into the soil. Mild infections can be asymptomatic, but more severe cases usually result in bloody diarrhea, and in rare cases, a prolapsed rectum, said Loke. More than 20 percent of patients end up having a colectomy in which a portion of the colon must be removed.

While whipworm infection is endemic in Asia, Africa and Latin America, it is rare in North America and northern Europe, where sewage systems generally interrupt transmission. Colitis, on the other hand, is generally nonexistent in those regions with widespread exposure, leading researchers to hypothesize that childhood exposure to these parasites might offer gastrointestinal protection against inflammatory bowel disease.

So far, the research has supported this theory, though the long-term safety of actively infecting patients with the worm is still unknown.

Because current medications for colitis and other bowel disorders are harsh, expensive and can come with negative side effects, people may see whipworms as a more natural, gentle solution, Mullin said, but these parasites carry their own risks.

The worms can cause microscopic bleeding in the intestines, which leads to anemia, said Mullin, and the immune response they incite is allergic in nature and could create complications for those with asthma or seasonal allergies. It's also impossible to know at this point what the side effects of inciting this kind of immune response will be 10 or more years down the road.

So while this patient's case study serves as a valuable educational tool for researchers, a whipworm cocktail is not advised for people living with colitis, doctors warned.

"What this patient did, while interesting, isn't recommended. We cannot assume from this one case study that taking human whipworm is going to be effective for everybody," Weinstock said.

"You don't want to encourage patients to go to underdeveloped countries and splash around in the mud and hope to get better. Indiscriminate exposure makes you liable to pick up other things."


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Sci Transl Med 1 December 2010:
Vol. 2, Issue 60, p. 60ra88
DOI: 10.1126/scitranslmed.3001500

IL-22+ CD4+ T Cells Are Associated with Therapeutic Trichuris trichiura Infection in an Ulcerative Colitis Patient

1. Mara J. Broadhurst1,*,
2. Jacqueline M. Leung2,*,
3. Vikram Kashyap2,
4. Joseph M. McCune1,
5. Uma Mahadevan3,
6. James H. McKerrow4 and
7. P’ng Loke2,†

+ Author Affiliations

1. 1Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143, USA.
2. 2Department of Medical Parasitology, New York University Langone Medical Center, New York, NY 10010, USA.
3. 3Division of Gastroenterology, Department of Medicine, Center for Colitis and Crohn’s Disease, University of California, San Francisco, CA 94143, USA.
4. 4Sandler Center for Basic Research in Parasitic Diseases, University of California, San Francisco, CA 94158, USA.

1. †To whom correspondence should be addressed. E-mail: png.loke@nyumc.org

1. ?* These authors contributed equally to this work.

Abstract

Ulcerative colitis, a type of inflammatory bowel disease, is less common in countries endemic for helminth infections, suggesting that helminth colonization may have the potential to regulate intestinal inflammation in inflammatory bowel diseases. Indeed, therapeutic effects of experimental helminth infection have been reported in both animal models and clinical trials. Here, we provide a comprehensive cellular and molecular portrait of dynamic changes in the intestinal mucosa of an individual who infected himself with Trichuris trichiura to treat his symptoms of ulcerative colitis. Tissue with active colitis had a prominent population of mucosal T helper (TH) cells that produced the inflammatory cytokine interleukin-17 (IL-17) but not IL-22, a cytokine involved in mucosal healing. After helminth exposure, the disease went into remission, and IL-22--producing TH cells accumulated in the mucosa. Genes involved in carbohydrate and lipid metabolism were up-regulated in helminth-colonized tissue, whereas tissues with active colitis showed up-regulation of proinflammatory genes such as IL-17, IL-13RA2, and CHI3L1. Therefore, T. trichiura colonization of the intestine may reduce symptomatic colitis by promoting goblet cell hyperplasia and mucus production through TH2 cytokines and IL-22. Improved understanding of the physiological effects of helminth infection may lead to new therapies for inflammatory bowel diseases.
Footnotes
*

Citation: M. J. Broadhurst, J. M. Leung, V. Kashyap, J. M. McCune, U. Mahadevan, J. H. McKerrow, P. Loke, IL-22+ CD4+ T Cells Are Associated with Therapeutic Trichuris trichiura Infection in an Ulcerative Colitis Patient Sci. Transl. Med. 2, 60ra88 (2010).

* Copyright (c) 2010, American Association for the Advancement of Science



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