Figure 3 S. mansoni modulation of the immune response. S. mansoni live helminth and antigens modify cells of the innate immune system through interaction with TLRs and CLRs arresting the production inﬂammatory mediators and eliciting instead, the release of immunoregulatory cytokines such as IL-10. This results in the generation of suppressive Treg and a bias towards a Th2 response. aaMΦ; alternately activated macrophage. Agent or product Schistosoma mansoni Schistosoma mansoni eggs Trichinella spiralis Trichuris suis Heligmosomoides polygyrus ES-62 (Acanthocheilonema viteae product) Table 4 Helminth infection or helminth products that prevent autoimmunity in animal models Volume 28, Number 10, October 2006 Parasitic worms and inﬂammatory diseases Reference (57) (58) (59) (60) (61) (62) (63) (64) 521 Autoimmune disease Experimental autoimmune encephalomyelitis Graves’ thyroiditis Experimental autoimmune encephalomyelitis Experimental colitis Experimental colitis Inﬂammatory bowel disease Experimental colitis Collagen-induced arthritis Infection with live helminth or challenge with their products (antigens, eggs etc.) can delay or prevent the induction of autoimmune disease in various disease models. (Inﬂammatory Bowel Disease) (65). Initial pilot studies using oral ingestion of live T. suis ova at regular intervals hinted at a beneﬁcial effect on IBD without any overt side- effects (62). Larger trials, including one double-blinded and placebo controlled, revealed effective relief of Crohn’s disease in nearly 80% of patients but much more modest effects in the case of Ulcerative Colitis (62,66). It should be noted that the patients enrolled in these studies were refractory to standard interventions, so any beneﬁcial effect should be welcomed, but larger trials with improved clinical scoring would be desirable (67). A similar trial, this time using the human hookworm Necator americanus, is also being carried out in Crohn’s patients (68). The caveat of a live parasite approach is only too evident; even if the chosen parasite is unable to productively infect the host patient, as is the case with T. suis, there may still be some adverse side-effects, particularly when patients are challenged in conjunction with immunosuppressants, or in otherwise immunosuppressed individuals. In particular, parasite-mediated immunomo- dulation may compromise the anti-tumour responsiveness of the patient (69–71). Far more desirable then would be to mimic the beneﬁcial effects of helminth infection by using non- infective products derived from them. Aside from the safety issues, the use of helminth products or their synthetic analogues © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Ltd, Parasite Immunology, 28, 515–523