Heligmosomoides polygyrus excretory/secretory products can protect against T-cell-mediated colitis through continuous delivery in vivo

Inflammatory bowel diseases (IBD) are becoming increasingly prevalent in affluent societies, but remain at low incidence in most tropical countries with higher rates of parasite infection. The possibility that parasites may inhibit the development of IBD has been raised in recent studies in both humans and mice showing successful suppression of IBD pathology with helminth parasites. In order to translate the anti-inflammatory effect seen with live parasite infection into a more pharmaceutical pipleline, we tested the capability of parasite secreted products, specifically excretory/secretory antigens (HES) from the gut dwelling helminth Heligmosomoides polygyrus, in suppressing colitis. To assess the effects of HES we utilised the adpotive transfer model of colitis, transferring na€ıve/effector T cells (sorted as CD4+CD25-FoxP3- cells from GFP-Foxp3 reporter mice) into RAGdeficient recipients. In this setting, colitis develops over 3–5 weeks. We also modified the administration of HES by implantation of i.p. mini-pumps capable of slow delivery of molecules osmotically over a two or 4 week time period. In this model, we now found that small concentrations of HES continuously released over the disease incubation period prevented the characteristic weight loss and reduced the histological damage seen in the untreated mice. Further studies are under way to evaluate if a therapeutic schedule of HES administration (given after the onset of mild colititic symptoms) and to testing of defined HES immunomodulators expressed as soluble recombinant proteins in mammalian expression systems.