5th Annual BMRP Investigator Meeting - Abstract

Hookworms as Therapy in Crohn’s Disease

Paul Fortun^1,a, Christopher Hawkey¹ and David Pritchard^2
 
1University Hospital and ²Immune Modulation Research Group, University of Nottingham (United Kingdom)

Crohn’s disease appears to be an imbalance between the body’s ability, through T cell networks, to control inflammation and immune tolerance. The balance between T helper 1 (Th1) and Th2 appears to be important: Th1 is associated with bacterial and viral infections, and autoimmune diseases, Th2 responses with helminth infections and allergy. Evidence in humans points to an excessive mucosal Th1 response to the enteric flora in inflammatory bowel disease, especially in Crohn’s disease. Parasites such as hookworm have developed anti-inflammatory molecular strategies to evade the host immunological response, which result in suppression of Th1 and stimulation of Th2. Helminth infection could therefore protect against Crohn’s disease.

Geographically, non-endemic regions of helminth infection are those where IBD is more common, yet migrants to the UK, especially Muslims, acquire a similar prevalence of Crohn’s disease to the local population after a few generations. It has been proposed that loss of parasite infection may be responsible. In mouse models of IBD, various helminth infections have been shown to ameliorate colitis, and protect against other autoimmune diseases. This has lead to several studies principally from the Weinstock’s group in Iowa into the effect of parasites on Crohn’s disease and subsequently ulcerative colitis.

The Th1/Th2 paradigm is probably too simplistic. A subset of negative regulators, the CD4+CD25+ regulatory T (Tr) cells and IL-10 producing Tr1 cells orchestrate Th1 and Th2 responses. Indeed, it has been demonstrated in a scid mouse model that low doses of Tr1 cells prevent IBD, whilst Th1 and Th2 cells had no effect.

The use of a zoonotic infection to ameliorate human autoimmune disease seems illogical: if the helminth and host have evolved together in a symbiotic rather than parasitic interaction, why not choose a human parasite? We are conducting a research program of human hookworm infection in the treatment of acute Crohn’s disease in a multicentre, placebo controlled trial. The study rationale and design will be outlined.

^aPrincipal Investigator