The use of Trichuris suis and other helminth therapies to treat Crohn’s disease

Infections with gastrointestinal (GI) nematodes are prevalent worldwide, despite the fact that anti-helminthic medications are regarded as safe, efficient, and widely available globally. In this review, we highlight the potential therapeutic benefits that may be realized through the clinical use of Trichuris suis and other helminths for Crohn’s disease (CD). Long-lived helminthic parasites are remarkable in their ability to down-regulate host immunity, protecting themselves from elimination, and also minimize severe pathological host changes. This review summarizes what is known about the underlying mechanisms that may account for the observed patterns in humans treated with helminths for CD. The Th2 arm of the immune system is emphasized as a component of primary importance in the association between the host immune system and GI nematode infections. Although GI nematode infections in humans cause significant morbidity and mortality, the existence and nature of protective mechanisms these helminths may confer remain largely unclear.

[1]  Ehrhardt Ro New insights into the immunopathology of chronic inflammatory bowel disease. , 1996 .

[2]  D. Elliott,et al.  Role of helminths in regulating mucosal inflammation , 2005, Springer Seminars in Immunopathology.

[3]  D. Elliott,et al.  Exposure to schistosome eggs protects mice from TNBS-induced colitis. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[4]  D. Elliott,et al.  Cutting Edge: Heligmosomoides polygyrus Induces TLR4 on Murine Mucosal T Cells That Produce TGFβ after Lipopolysaccharide Stimulation1 , 2006, The Journal of Immunology.

[5]  F. Murad,et al.  Down-regulation of inducible nitric-oxide synthase (NOS-2) during parasite-induced gut inflammation: a path to identify a selective NOS-2 inhibitor. , 2001, Molecular pharmacology.

[6]  E. Loftus,et al.  True or False? The Hygiene Hypothesis for Crohn's Disease , 2006, The American Journal of Gastroenterology.

[7]  Robert W. Summers,et al.  Vomiting in the recently anticoagulated patient , 2004, Gut.

[8]  P. Hasler Biological therapies directed against cells in autoimmune disease , 2006, Springer Seminars in Immunopathology.

[9]  F. Guarner,et al.  Mechanisms of Disease: the hygiene hypothesis revisited , 2006, Nature Clinical Practice Gastroenterology &Hepatology.

[10]  D. Elliott,et al.  Does the failure to acquire helminthic parasites predispose to Crohn's disease? , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  W. Sandborn,et al.  Advances in the treatment of Crohn's disease. , 2004, Gastroenterology.

[12]  B. Scott,et al.  How effective are the usual treatments for Crohn's disease? , 2004, Alimentary pharmacology & therapeutics.

[13]  R. Ehrhardt New insights into the immunopathology of chronic inflammatory bowel disease. , 1996, Seminars in gastrointestinal disease.

[14]  J. Aliberti,et al.  Anti-inflammatory pathways as a host evasion mechanism for pathogens. , 2005, Prostaglandins, leukotrienes, and essential fatty acids.

[15]  H. Helmby Immunity to gastrointestinal nematodes: a story of immune modulation , 2005, Expert review of clinical immunology.

[16]  D. McKay,et al.  Helminths as therapeutic agents for inflammatory bowel disease , 2004 .

[17]  T. Moreels,et al.  Gastrointestinal Parasites: Potential Therapy for Refractory Inflammatory Bowel Diseases , 2005, Inflammatory bowel diseases.

[18]  I. Oswald Role of intestinal epithelial cells in the innate immune defence of the pig intestine. , 2006, Veterinary research.

[19]  L V Kirchhoff,et al.  American trypanosomiasis (Chagas' disease)--a tropical disease now in the United States. , 1993, The New England journal of medicine.

[20]  J. Weinstock Helminths and Mucosal Immune Modulation , 2006, Annals of the New York Academy of Sciences.

[21]  Maria Yazdanbakhsh,et al.  Allergy, parasites, and the hygiene hypothesis. , 2002, Science.

[22]  M. Cheang,et al.  A Population-Based Case Control Study of Potential Risk Factors for IBD , 2006, The American Journal of Gastroenterology.

[23]  D. Elliott,et al.  Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGFbeta after lipopolysaccharide stimulation. , 2006, Journal of immunology.

[24]  F L STONE,et al.  TWO SIDES OF THE COIN. , 1963, Journal of medical education.

[25]  P. Marteau,et al.  Mesalamine in the treatment of active Crohn's disease. , 2005, Gastroenterology.

[26]  D. Wakelin,et al.  Immunopathology of intestinal helminth infection , 2000, Parasite immunology.

[27]  G. Oppenheimer,et al.  Landmark article Oct 15, 1932. Regional ileitis. A pathological and clinical entity. By Burril B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer. , 1984, JAMA.

[28]  J. Tjandra,et al.  Long-term follow-up of strictureplasty in Crohn's disease , 1993, Diseases of the colon and rectum.

[29]  F. Zavala,et al.  Immunology of malaria infections , 2006, Parasite immunology.

[30]  G. Oppenheimer,et al.  Regional ileitis; a pathologic and clinical entity. , 1952, The American journal of medicine.

[31]  Rick M. Maizels,et al.  Immune Regulation by helminth parasites: cellular and molecular mechanisms , 2003, Nature Reviews Immunology.

[32]  A. Cooke,et al.  Parasitic worms and inflammatory diseases , 2006, Parasite immunology.

[33]  A. McKenzie,et al.  Helminth-Modified Pulmonary Immune Response Protects Mice from Allergen-Induced Airway Hyperresponsiveness1 , 2006, The Journal of Immunology.

[34]  Sunetra Gupta,et al.  Parasite immune escape: new views into host-parasite interactions. , 2005, Current opinion in microbiology.

[35]  D. Elliott,et al.  Helminths and harmony , 2003, Gut.

[36]  D. Elliott,et al.  Is there a role for helminths in the therapy of inflammatory bowel disease? , 2005, Nature Clinical Practice Gastroenterology &Hepatology.

[37]  Judy H. Cho,et al.  Inflammatory Bowel Disease Characteristics Among African Americans, Hispanics, and Non-Hispanic Whites: Characterization of a Large North American Cohort , 2006, The American Journal of Gastroenterology.

[38]  R. Sartor Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis , 2006, Nature Clinical Practice Gastroenterology &Hepatology.

[39]  A. Khan,et al.  Selective effector mechanisms for the expulsion of intestinal helminths , 1994, Parasite immunology.

[40]  D. Elliott,et al.  Why Trichuris suis should prove safe for use in inflammatory bowel diseases. , 2005, Inflammatory Bowel Diseases.

[41]  C. Kelly,et al.  Interleukin 16 is up-regulated in Crohn's disease and participates in TNBS colitis in mice. , 2000, Gastroenterology.

[42]  D. Kristan Maternal and direct effects of the intestinal nematode Heligmosomoides polygyrus on offspring growth and susceptibility to infection. , 2002, The Journal of experimental biology.

[43]  R. Blumberg,et al.  Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. , 1999, Current opinion in immunology.

[44]  D. Elliott,et al.  Helminths and the modulation of mucosal inflammation , 2005, Current opinion in gastroenterology.