Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis

Abstract

SummaryInflammatory bowel disease (IBD) is the most common and serious chronic inflammatory condition of the gut. Among the distinct T helper (Th) cell subsets, a Th1 type response is associated predominantly with Crohn's disease (CD) while helminth infections generate a strong Th2 type response. IBD is most prevalent in developed countries but rare in countries where infections with helminths are common. Thus, it has been hypothesized that infection with helminth infection influence the development of CD and recent clinical and experimental studies suggest strongly a beneficial role of helminth infection in IBD. In the present study we examined the effects of rectal submucosal administration of helminth antigens on subsequent experimental colitis. Mice were treated with Trichinella spiralis antigens prior to the induction of dinitrobenzenesulphonic acid (DNBS)-induced colitis and were killed 3 days post-DNBS to assess colonic damage macroscopically, histologically and by myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) and cytokine levels. Previous treatment with T. spiralis antigens reduced the severity of colitis significantly, as assessed macroscopically and histologically, and reduced the mortality rate. This benefit was correlated with a down-regulation of MPO activity, interleukin (IL)-1b production and iNOS expression and an up-regulation of IL-13 and transforming growth factor-b production in colon. These results clearly show a beneficial role of local treatment with helminth antigens for experimental colitis and prompt consideration of helminth antigen-based therapy for IBD instead of infection with live parasites.

Extracts of the Rat Tapeworm,Hymenolepis diminuta, Suppress Macrophage ActivationIn Vitroand Alleviate Chemically Induced Colitis in Mice

“…So while the precise mechanism of action of HdHMW is unclear, this is, to our knowledge, the first demonstration of the ability of a cestode-derived extract to inhibit murine colitis. As such it complements recent studies showing that undefined extracts of Trichinella spiralis and S. mansoni reduce the severity of trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice (30,31) and those showing that that S. mansoni soluble egg antigen, Acanthocheilonema viteae ES-62, and a PBS-soluble extract of Ascaris suum can inhibit colitis, arthritis, and asthma in murine model systems (8,18,27,36).…”

Gut Inflammation: Current Update on Pathophysiology, Molecular Mechanism and Pharmacological Treatment Modalities

“…Similar beneficial effect was observed in patients with UC (improvement: 47.3 % vs. 16.7 % placebo) [339,340]. Recent experimental results showed a beneficial effect of the local treatment with Trichinella spiralis antigens in experimental colitis induced by dinitrobenzene sulfonic acid in mice, which suggest that helminth antigen-based therapy should be applied for IBD instead of infection with live parasites [341].…”

Hookworm Excretory/Secretory Products Induce Interleukin-4 (IL-4)+IL-10+CD4+T Cell Responses and Suppress Pathology in a Mouse Model of Colitis

“…A growing body of literature suggests that much of this protection against inflammation is mediated by soluble molecules released by the parasites. Some examples include protection in the dinitrobenzene sulfonic acid (DNBS) model of colitis utilizing soluble somatic extracts from Trichinella spiralis (34) and Hymenolepis diminuta (35), as well as the use of ES products from Ancylostoma ceylanicum, a relative of A. caninum, in the DSS model of colitis (36). Furthermore, AcES and Schistosoma mansoni somatic proteins alleviated pathology associated with TNBSmediated colitis (22).…”