TSO Theory

Theory, Basic Science and Inventors
Over the last decade several research teams have uncovered a possible explanation for the dramatic rise in autoimmune disease and allergy that has occurred in industrialized countries. Many diseases such as Crohn’s disease, ulcerative colitis, multiple sclerosis, rheumatoid arthritis, insulin-dependent (Type 1) diabetes and asthma became much more prevalent during the last half of the twentieth century (1). The increase in prevalence for these diseases occurred in conjunction with increases in standard of living and hygienic conditions. These types of immune-mediated diseases remain rare in less developed tropical countries. It is clear that a change in our environment has promoted development of immune-mediated disease. Many changes in our environment have occurred. One of the most significant, from an immunologic standpoint, is the eradication of exposure to helminthic parasites (2). These complex organisms have far-reaching effects on the immune system that could prevent development or inhibit expression of autoimmune disease (3).Basic studies using animal models of human disease have shown that exposure to helminths can prevent colitis (1, 4-7), autoimmune diabetes (8,9), and autoimmune encephalitis (10, 11). Recently, investigators at the University of Iowa have shown that exposure to intestinal worms can reverse established colitis in IL-10 deficient mice (12). These studies suggest that exposure to helminths may be able to prevent or treat human disease.

(1) Bach, J.F. The effect of infections on susceptibility to autoimmune and allergic diseases. New England Journal of Medicine 347:911, 2002.

(2) Elliott, D.E., J.F.J. Urban, C.K. Argo, and J.V. Weinstock. Does the failure to acquire helminthic parasites predispose to Crohn’s disease? FASEB Journal 14:1848, 2000.

(3) Maizels RM,and Yazdanbakhsh M. Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews Immunology. 3:733, 2003.

(4) Reardon C, Sanchez A, Hogaboam CM, and McKay DM. Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium-induced colitis. Infection & Immunity 69:4417, 2001.

(5) Elliott, D.E., Li J, Blum A, Metwali A, Qadir K, Urban J.F., Jr., and Weinstock J.V. Exposure to Schistosome Eggs protects mice from TNBS-induced colitis. American Journal of Physiology 284:G385, 2003.

(6) Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, and Collins SM. Intestinal nematode infection ameliorates experimental colitis in mice. Infection & Immunity 70:5931, 2002.

(7) Moreels TG, Nieuwendijk RJ, De Man JG, De Winter BY, Herman AG, Van Marck EA, and Pelckmans PA. 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, 2004.

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

(9) Zaccone P. Fehervari Z. Jones FM. Sidobre S. Kronenberg M. Dunne DW. And Cooke A. Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. European Journal of Immunology. 33:1439-49, 2003.

(10) Sewell D, Qing Z, Reinke E, Elliott D, Weinstock J, Sandor M, Fabry Z. Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. International Immunology 15:59-69, 2003.

(11) La Flamme AC, Ruddenklau K, Backstrom BT. Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infection & Immunity 71:4996-5004, 2003.

(12) Elliott DE, Setiawan T, Metwali A, Blum A, Urban JFJ, and Weinstock J.V. H. polygyrus inhibits established colitis in IL10 deficient mice. Eur.J.Immunol. 34:2690, 2004.With much thanks we would like to honor and acknowledge the scientific work of the Inventors of the Helminth Therapy to:

Prof. Joel V. Weinstock, M.D.
Director, Division of Gastroenterology-HepatologyDirector, Center for Digestive Diseases
Dr. Weinstock’s research interest is the immunoregulation of granulomatous inflammation. His studies examine the role of peptide neurokines and lymphokines in the regulation of inflammation. He also examines the response of the mucosal immune system to granulomatous stimuli. His clinical research interests are inflammatory bowel disease and schistosomiasis.
Dr. Weinstock is particularly interested in immunology, immunoregulation, granulomatous inflammation, schistosomiasis, inflammatory bowel diseases, lymphokines, and T cell receptors.

Honors, Awards, and Organizations
Alpha Omega AlphaAmerican Association for the Study of Liver DiseaseAmerican Association of ImmunologistsAmerican Federation for Clinical Research, Senator, 1983American Gastroenterological AssociationAmerican Institute of NutritionAmerican Society for Gastrointestinal EndoscopyAmerican Society of Clinical InvestigationAmerican Society of Clinical NutritionCentral Immunology SocietyCentral Society for Clinical ResearchMidwest Gut ClubCrohn’s and Colitis Foundation of America, Scientific Advisor

Recent Publications
Wickelgren, I. Immunotherapy: Can Worms Tame the Immune System? Science 2004 305:170-171.Metwali, A., Blum, A.M., Elliott, D.E., Setiawan, T., and Weinstock, J.V.: Hemokinin Has Substance P Like Function and Expression in Inflammation. J. Immunol. (Cutting Edge) 2004 172: 6528-6532.Weinstock, J.V., Summers, R., and Elliott, D.E.: Helminths and harmony. Commentary: Helminths. Gut, 53:7-9, 2004.Click here for additional publications.

Links of Interest
Community of Science Profile Questions on Research on Potential Helminthic Therapy of Inflammatory Bowel Disease James A. Clifton Center for Digestive Diseases

Prof. David Elliott, M.D., Ph.D.
Associate Professor

Dr. Elliott’s research interest focuses on the mechanisms that control inflammatory reactions. His studies include the liver granulomas that develop in murine schistosomiasis; the role of the neuropeptide somatostatin in the regulation of the granulomatous response; and soluble mediators released by granuloma cells that affect inflammatory responses. He employs the ELISA assays of lymphokine production, cellular cloning, Northern blot analysis of granuloma mRNA, reverse transcription PCR or granuloma lymphocyte mRNA, RNASE protection assays, and molecular cloning. His key interests are immunology, immunoregulation, granulomatous inflammation, schistosomiasis, and inflammatory bowel diseases, lymphokines, T cell receptor.

Medical School:Wayne State University
Residency:Johns Hopkins University
Fellowship:The University of Iowa
Graduate School:Wayne State University

Links of Interest
Community of Science ProfileQuestions on Research on Potential Helminthic Therapy of Inflammatory Bowel Disease Prof. Robert W. Summers, M.D.
James A. Clifton Professor and Director of Clinical Programs for the Gastroenterology DivisionDr. Summers is well known for his work on small bowel motor activity. He has studied the effects of irradiation on the smooth muscle of both the small and large intestine. His ongoing clinical studies include the examination of therapeutic agents in motility disorders and inflammatory bowel disease; aspirin and folic acid in the prevention of colonic polyps; and the effects of exercise on intestinal function.
Dr. Summers is particularly interested in gastrointestinal motility disorders; mechanisms of injury in radiation enteritis; colon cancer; and inflammatory bowel diseases.
Honors, Awards, and Organizations
American Association for the Study of Liver DiseaseDiplomate, American Board of Internal Medicine, and Board of GastroenterologyAmerican Board of Internal Medicine: Member, Gastroenterology Board of Examiners, 1979-85American College of Physicians: FellowAmerican Federation for Clinical ResearchAmerican Gastroenterology Association,American Motility Society , President 1998-2000American Physiological SocietyAmerican Society for Gastrointestinal EndoscopyBurroughs-Wellcome Research Travel Grant Recipient, 1979Central Society for Clinical ResearchCrohn’s and Colitis Foundation of AmericaGastroenterology Research GroupIowa Foundation for Medical CareJanssen Research CouncilMidwest Gut ClubUSPHS Fogarty Fellowship in Gastrointestinal Physiology, 1980-

Recent Publications
Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, Stone E, Aaltonen LA: Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science, 280:1086-1088, 1998.Ryan AJ, Lambert GP, Shi X, Chang RT, Summers RW, Gisolfi CV: Effect of hypohydration on gastric emptying and intestinal absorption during exercise. J. Appl Physiol, 84:1581-1588, 1998.Summers, RW. Approach to the Patient with Ileus and Obstruction, In: Textbook of Gastroenterology, 3rd ed., Yamada T, Alpers DH, Laine S, Owyang C, Powell DW (ed.). Lippincott Williams & Williams, Philadelphia, PA, 1999.Links of Interest
Community of Science ProfileQuestions on Research on Potential Helminthic Therapy of Inflammatory Bowel Disease

TSO Theory

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