Skip to main content
SpringerLink
Log in
Book cover

Nature Helps... pp 211–225Cite as

Helminth Therapy to Treat Crohn’s and Other Autoimmune Diseases

  • Chapter
  • First Online:

Part of the book series: Parasitology Research Monographs ((Parasitology Res. Monogr.,volume 1))

Abstract

This review updates a previous one (Reddy and Fried, Parasitol Res 104:217–221, 2009) on Crohn’s and other autoimmune diseases and helminth therapy. Our review considers the use of various helminths or their worm products to treat the following autoimmune diseases: Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis, Type-1 Diabetes, and Asthma and allergic disorders. The use of the following helminths or their worm products are considered in this review: the nematodes Trichuris suis, Necator americanus, Heligomosomoides polygyrus, Trichinella spiralis, Ancanthocheilonema viteae, Ascaris suum, Nippostrongylus brasiliensis, Syphacia obvelata, Dirofilaria immitis, Litomosoides sigmodontis; the cestodes Hymenolepis diminuta and Taenia crassiceps; and the trematodes Schistosoma mansoni, Schistosoma japonicum, and Fasciola hepatica. Our review discusses the potential role of worm products rather than live worms in future studies using helminths to treat autoimmune diseases.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Alic M (2000) Inflammatory bowel diseases are diseases of higher socioeconomic status: dogma or reality? Am J Gastroenterol 95:3332–3333

    Article  PubMed  CAS  Google Scholar 

  • Bager P, Arnved J, Ronborg S, Wohlfahrt J, Poulsen LK, Westergaard T, Petersen HW, Kristensen B, Thamsborg S, Roepstorff A, Kapel C, Melbye M (2010) Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. J Allergy Clin Immunol 125:123–130

    Article  PubMed  Google Scholar 

  • Braus NA, Elliott DE (2009) Advances in the pathogenesis and treatment of IBD. Clin Immunol 132:1–9

    Article  PubMed  CAS  Google Scholar 

  • Cooke A, Tonks P, Jones FM, O’Shea H, Hutchings P, Fulford AJC, Dunne DW (1999) Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol 21:169–176

    Article  PubMed  CAS  Google Scholar 

  • Correale J, Farez M (2007) Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol 61:97–108

    Article  PubMed  CAS  Google Scholar 

  • Correale J, Mauricio F (2009) Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms. J Immunol 183:5999–6012

    Article  PubMed  CAS  Google Scholar 

  • Correale J, Farez M, Razzite G (2008) Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol 64:187–199

    Article  PubMed  Google Scholar 

  • Croese J, O’Neil J, Masson J, Cooke S, Melrose W, Pritchard D, Speare R (2006) A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors. Gut 55:136–137

    Article  PubMed  CAS  Google Scholar 

  • Dittrich AM, Erbacher A, Specht S, Diesner F, Krokowski M, Avagyan A, Stock P, Ahrens B, Hoffmann WH, Hoerauf A, Hamelmann E (2008) Helminth infection with Litomosoides sigmodontis induces regulatory T cells and inhibits allergic sensitization, airway inflammation, and hyperreactivity in a murine asthma model. J Immunol 180:1792–1799

    PubMed  CAS  Google Scholar 

  • Ehrhardt RO (1996) New insights into the immunopathology of chronic inflammatory bowel disease. Semin Gastrointest Dis 7:144–150

    PubMed  CAS  Google Scholar 

  • Elliott DE, Li J, Blum A, Metwali A, Qadir K, Urban JF Jr, Weinstock JV (2003) Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol 284:385–391

    Google Scholar 

  • Elliott DE, Setiawan T, Metwali A, Blum A, Urban JF Jr, Weinstock JV (2004) Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice. Eur J Immunol 34:2690–2698

    Article  PubMed  CAS  Google Scholar 

  • Elliott DE, Summers RW, Weinstock JV (2005) Helminths and the modulation of mucosal inflammation. Curr Opin Gastroenterol 21:51–58

    PubMed  Google Scholar 

  • Espinoza-Jimenez A, Rivera-Montoya I, Cardenas Arreola R, Moran L, Terrazas LI (2010) Taenia crassiceps infection attenuates multiple low-dose streptozotocin-induced diabetes. J Biomed Biotechnol. doi:10.1155/2010/850541

    PubMed  Google Scholar 

  • Folkerts G, Walzl G, Openshaw PJM (2000) Do common childhood infections ‘teach’ the immune system not to be allergic? Immunol Today 21:118–120

    Article  PubMed  CAS  Google Scholar 

  • Fukumoto S, Iriko H, Otsuki H (2009) Helminth infections prevent autoimmune diseases through Th2-type immune response. Yonago Acta Med 52:85–104

    Google Scholar 

  • Gale EA (2002) The rise of childhood type 1 diabetes in the 20th century. Diabetes 51:3353–3361

    Article  PubMed  CAS  Google Scholar 

  • Gruden-Movsesijan A, Ilic N, Mostarica Stojkovic M, Stosic-Grujicic S, Milic M, Sofronic-Milosavljevic L (2008) Trichinella spiralis: modulation of experimental autoimmune encephalomyelitis in DA rats. Exp Parasitol 118:641–647

    Article  PubMed  CAS  Google Scholar 

  • Harnett W, Harnett MM, Byron O (2003) Structural/functional aspects of ES-62: a secreted immunomodulatory phosphorylcholine-containing filarial nematode glycoprotein. Curr Prot Peptide Sci 4:59

    Article  CAS  Google Scholar 

  • Harnett MM, Kean DE, Boitelle A, McGuiness S, Thalhamer T, Steiger CN, Egan C, Al-Riyami L, Alcocer MJ, Houston KM, Gracie JA, McInnes IB, Harnett W (2008) The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis. Ann Rheum Dis 67:518–523

    Article  PubMed  CAS  Google Scholar 

  • Hübner MP, Stocker JT, Mitre E (2009) Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells. Immunology 127:512–522

    Article  PubMed  Google Scholar 

  • Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK (2008) IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol 180:2443–2449

    PubMed  CAS  Google Scholar 

  • Hunter MM, Wang A, McKay D (2007) Helminth infection enhances disease in a murine TH2 model of colitis. Gastroenterology 132:1320–1330

    Article  PubMed  CAS  Google Scholar 

  • Hunter MM, Wang A, Parhar KS, Johnston MJG, Van Rooijen N, Beck PL, McKay DM (2010) In vitro-derived alternatively activated macrophages reduce colonic inflammation in mice. Gastroenterology 138:1395–1405

    Article  PubMed  CAS  Google Scholar 

  • Imai S, Tezuka H, Fujita K (2001) A factor of inducing IgE from a filarial parasite prevents insulin-dependent diabetes mellitus in nonobese diabetic mice. Biochem Biophys Res Commun 286:1051–1058

    Article  PubMed  CAS  Google Scholar 

  • Itami DM, Oshiro TM, Araujo CA, Perini A, Martins MA, Macedo MS, Macedo-Saores MF (2005) Modulation of murine experimental asthma by Ascaris suum components. Clin Exp Allergy 35:873–879

    Article  PubMed  CAS  Google Scholar 

  • Johnston MJG, Wang A, Catarino MED, Ball L, Phan VC, MacDonald JA, McKay DM (2010) Extracts of the rat tapeworm, Hymenolepis diminuta, suppress macrophage activation in vitro and alleviate chemically induced colitis in mice. Infect Immunol 78:1364–1375

    Article  CAS  Google Scholar 

  • Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, Collins SM (2002) Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immunol 70:5931–5937

    Article  CAS  Google Scholar 

  • Kuijk LM, Van Die I (2010) Worms to the rescue: can worm glycans protect from autoimmune diseases? Life 62:303–312

    PubMed  CAS  Google Scholar 

  • Kurtzke JF (2000) Multiple sclerosis in time and space – geographic clues to cause. J Neurovirol 6:S134–S140

    PubMed  Google Scholar 

  • La Flamme AC, Ruddenklau K, Backstrom BT (2003) Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immunol 71:4996–5004

    Article  Google Scholar 

  • Liu Q, Sundar K, Mishra PK, Mousavi G, Liu ZG, Gaydo A, Alem F, Lagunoff D, Bleich D, Gause WC (2009) Helminth infection can reduce insulitis and type 1 diabetes through CD25- and IL-10-independent mechanisms. Infect Immunol 77:5347–5358

    Article  CAS  Google Scholar 

  • Mangan NE, Fallon RE, Smith P, Van Rooijen N, McKenzie AN, Fallon PG (2004) Helminth infection protects mice from anaphylaxis via IL-10-producing B cells. J Immunol 173:6346–6356

    PubMed  CAS  Google Scholar 

  • Mangan NE, Van Rooijen N, McKenzie ANJ, Fallon PG (2006) Helminth-modified pulmonary immune response protects mice from allergen-induced airway hyperresponsiveness. J Immunol 176:138–147

    PubMed  CAS  Google Scholar 

  • McFarland HF, Martin R (2007) Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 8:913–919

    Article  PubMed  CAS  Google Scholar 

  • McInnes IB, Leung BP, Harnett M, Gracie JA, Liew FY, Harnett W (2003) A novel therapeutic approach targeting articular inflammation using the filarial nematode-derived phosphorylcholine-containing glycoprotein ES-62. J Immunol 171:2127–2133

    PubMed  CAS  Google Scholar 

  • Mo HM, Liu WQ, Lei JH, Cheng YL, Wang CZ, Li YL (2007) Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent development of colitis in mice. Exp Parasitol 116:385–389

    Article  PubMed  CAS  Google Scholar 

  • Moreels TG, Nieuwendijk RJ, De Man JG, De Winter BY, Herman AG, Van Marck EA, Pelckmans PA (2004) Concurrent infection with Schistosoma mansoni attenuates inflammation induced changes in colonic morphology, cytokine levels, and smooth muscle contractility of trinitrobenzene sulphonic acid induced colitis in rats. Gut 53:99–107

    Article  PubMed  CAS  Google Scholar 

  • Motomura Y, Wang H, Deng Y, El-Sharkawy RT, Verdu EF, Khan WI (2009) Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis. Clin Exp Immunol 155:88–95

    Article  PubMed  CAS  Google Scholar 

  • Onkamo P, Vaananen S, Karvonen M, Tuomilehto J (1999) Worldwide increase in incidence of type 1 diabetes – the analysis of the data on published incidence trends. Diabetologia 42:1395–1403

    Article  PubMed  CAS  Google Scholar 

  • Osada Y, Kanazawa T (2010) Parasitic helminths: new weapons against immunological disorders. J Biomed Biotechnol. doi:10.1155/2010/743758

    PubMed  Google Scholar 

  • Osada Y, Shimizu S, Kumagai T, Yamada S, Kanazawa T (2009) Schisosoma mansoni infection reduces severity of collagen-induced arthritis via down-regulation of proinflammatory mediators. Int J Parasitol 39:457–464

    Article  PubMed  CAS  Google Scholar 

  • Pearson DJ, Taylor G (1975) The influence of the nematode Syphacia oblevata on adjuvant arthritis in the rat. Immunology 29:391–396

    PubMed  CAS  Google Scholar 

  • Reddy A, Fried B (2007) The use of Trichuris suis and other helminth therapies to treat Crohn’s disease. Parasitol Res 100:921–927

    Article  PubMed  Google Scholar 

  • Reddy A, Fried B (2009) An update on the use of helminths to treat Crohn’s and other autoimmune diseases. Parasitol Res 104:217–221

    Article  PubMed  Google Scholar 

  • Rocha FAC, Leite AKRM, Pompeu MML, Cunha TM, Verri WA, Soares FM, Castro RR, Cunha FQ (2008) Protective effect of an extract from Ascaris suum in experimental arthritis models. Infect Immunol 76:2736–2745

    Article  CAS  Google Scholar 

  • Ruyssers NE, De Winter BY, De Man JG, Loukas A, Pearson MS, Weinstock JV, Van den Bossche RM, Martinet W, Pelckmans PA, Moreels TG (2009) Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis 15:491–500

    Article  PubMed  Google Scholar 

  • Ruyssers NE, De Winter BY, De Man JG, Ruyssers ND, Van Gils AJ, Loukas A, Pearson MS, Weinstock JV, Pelckmans PA, Moreels TG (2010) Schistosoma mansoni proteins attenuate gastrointestinal motility disturbances during experimental colitis in mice. World J Gastroentrol 16:703–712

    Article  CAS  Google Scholar 

  • Salinas-Carmona MC, De la Cruz-Galacia G, Perez-Rivera I, Solis-Soto JM, Segoviano-Ramirez JC, Vazquez AV, Garza MA (2009) Spontaneous arthritis in MRL/lpr mice is aggravated by Staphylococcus aureus and ameliorated by Nippostrongylus brasiliensis infections. Autoimmunity 42:25–32

    Article  PubMed  CAS  Google Scholar 

  • Sartor RB (2006) Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Prac Gastroenterol Hepatol 3:390–407

    Article  CAS  Google Scholar 

  • Saunders KA, Raine T, Cooke A, Lawrence CE (2007) Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immunol 75:397–407

    Article  CAS  Google Scholar 

  • Schaub B, Lauener R, von Mutius E (2006) The many faces of the hygiene hypothesis. J Allergy Clin Immunol 117:969–977

    Article  PubMed  Google Scholar 

  • Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M, Fabry Z (2003) Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol 15:59–69

    Article  PubMed  CAS  Google Scholar 

  • Smith P, Mangan NE, Walsh CM, Fallon RE, McKenzie AN, Van Rooijen N, Fallon PG (2007) Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol 178:4557–4566

    PubMed  CAS  Google Scholar 

  • Smits HH, Everts B, Hartgers FC, Yazdanbakhsh M (2010) Chronic Helminth infections protect against allergic diseases by active regulatory processes. Curr Allergy Asthma Rep 10:3–12

    Article  PubMed  Google Scholar 

  • Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV (2005a) Trichuris suis therapy in Crohn’s disease. Gut 54:87–90

    Article  PubMed  CAS  Google Scholar 

  • Summers RW, Elliott DE, Weinstock JV (2005b) Is there a role for helminths in the therapy of inflammatory bowel disease? Nat Clin Prac Gastroenterol Hepatol 2:62–63

    Article  Google Scholar 

  • Summers RW, Elliott DE, Weinstock JB (2005c) Why Trichuris suis should prove safe for use in inflammatory bowel diseases. Inflamm Bowel Dis 11:783–784

    Article  PubMed  Google Scholar 

  • Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV (2006) Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128:825–832

    Article  Google Scholar 

  • Tisch R, McDevitt H (1996) Insulin-dependent diabetes mellitus. Cell 85:291–297

    Article  PubMed  CAS  Google Scholar 

  • Van Kruiningen HJ, West AB (2005) Potential danger in the medical use of Trichuris suis for the treatment of inflammatory disease. Inflamm Bowel Dis 11:515

    Article  PubMed  Google Scholar 

  • Walsh KP, Brady MT, Finlay CM, Boon L, Mills KH (2009) Infection with a helminth parasite attenuates autoimmunity through TGF-β-mediated suppression of Th17 and Th1 responses. J Immunol 183:1577–1586

    Article  PubMed  CAS  Google Scholar 

  • Weinstock JV, Summers RW, Elliott DE (2005) Role of helminths in regulating mucosal inflammation. Springer Semin Immunopathol 27:249–271

    Article  PubMed  Google Scholar 

  • Wilson MS, Taylor MD, Balic A, Finney CAM, Lamb JR, Maizels RM (2005) Suppression of allergic airway inflammation by helminth-induced regulatory T cells. J Exp Med 202:1199–1212

    Article  PubMed  CAS  Google Scholar 

  • Yang JH, Zhao JQ, Yang YF, Zhang L, Yang X, Zhu X, Ji MJ, Sun NX, Su C (2006) Schistosoma japonicum egg antigens stimulate CD4+CD25+ T cells and modulate airway inflammation in a murine model of asthma. Immunology 120:8–18

    PubMed  Google Scholar 

  • Yoshimoto T, Nakanishi K (2006) Roles of IL-18 in basophils and mast cells. Allergol Int 55:105–113

    Article  PubMed  CAS  Google Scholar 

  • Zaccone P, Cooke A (2010) Harnessing CD8+ regulatory T cells: therapy for type-1 diabetes? Immunity 32:504–506

    Article  PubMed  CAS  Google Scholar 

  • Zaccone P, Fehervari Z, Jones FM, Sidobre S, Kronenberg M, Dunne DW, Cooke A (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol 33:1439–1449

    Article  PubMed  CAS  Google Scholar 

  • Zaccone P, Burton O, Miller N, Jones FW, Dunne DW, Cooke A (2009) Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice. Eur J Immunol 39:1098–1107

    Article  PubMed  CAS  Google Scholar 

  • Zheng X, Hu X, Zhou G, Lu Z, Qiu W, Bao J, Dai Y (2008) Soluble egg antigen from Schistosoma japonicum modulates the progression of chronic progressive experimental autoimmune encephalomyelitis via Th2-shift response. J Neuroimmunol 194:107–114

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Lafayette College, Easton, PA, 18042, USA

    Jeff Bolstridge

  2. Department of Biology, Lafayette College, Easton, PA, 18042, USA

    Bernard Fried & Aditya Reddy

Authors
  1. Jeff Bolstridge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernard Fried
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aditya Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard Fried .

Editor information

Editors and Affiliations

  1. Department of Zoomorphology, Cell Biology and Parasitology,, Heinrich Heine University, Universitätsstr. 1, Düsseldorf, 40225, Germany

    Heinz Mehlhorn

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bolstridge, J., Fried, B., Reddy, A. (2011). Helminth Therapy to Treat Crohn’s and Other Autoimmune Diseases. In: Mehlhorn, H. (eds) Nature Helps.... Parasitology Research Monographs, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-19382-8_9

Download citation

Publish with us

Policies and ethics

Search

Navigation