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Background Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied. Objective The aim was to investigate whether infection with the nematode parasite Trichuris suis alters systemic cytokine levels, cellular cytokine responses to parasite antigens and pollen allergens and/or the cytokine profile of allergic individuals. Methods In a randomized double-blinded placebo-controlled clinical trial (UMIN trial registry, Registration no. R000001298, Trial ID UMIN000001070, URL: http://www.umin.ac.jp/map/english), adults with grass pollen-induced allergic rhinitis received three weekly doses of 2500 Trichuris suis ova (n = 45) or placebo (n = 44) over 6 months. IFN-γ, TNF-α, IL-4, IL-5, IL-10 and IL-13 were quantified via cytometric bead array in plasma. Cytokines, including active TGF-β, were also quantified in supernatants from peripheral blood mononuclear cells cultured with parasite antigens or pollen allergens before, during and after the grass pollen season for a sub-cohort of randomized participants (T. suis ova-treated, n = 12, Placebo-treated, n = 10). Results Helminth infection induced a Th2-polarized cytokine response comprising elevated plasma IL-5 and parasite-specific IL-4, IL-5 and IL-13, and a global shift in the profile of systemic cytokine responses. Infection also elicited high levels of the regulatory cytokine IL-10 in response to T. suis antigens. Despite increased production of T. suis-specific cytokines in T. suis ova-treated participants, allergen-specific cytokine responses during the grass pollen season and the global profile of PBMC cytokine responses were not affected by T. suis ova treatment. Conclusions and clinical relevance This study suggests that cytokines induced by Trichuris suis ova treatment do not alter allergic reactivity to pollen during the peak of allergic rhinitis symptoms.

UnlabelledSymptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3(rd) dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was ≤ 14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation.Trial registrationUniversity hospital Medical Information Network trial registry Reg. no. R000001298, Trial ID UMIN000001070.

Parasitic helminth infections can protect against allergic airway inflammation in experimental models and have been associated with a reduced risk of atopy and a reduced course of asthma in some observational studies. Although no clinical evidence exists to support the use of helminth therapy for allergic disease, the helminth Trichuris suis has demonstrated efficacy in treatment of inflammatory bowel disease.To determine efficacy of helminth therapy for allergic rhinitis.We conducted a double-blind, placebo-controlled, parallel group trial in which 100 subjects age 18 to 65 years with grass pollen-induced allergic rhinitis were randomly assigned to ingest a total of 8 doses with 2500 live T suis ova or placebo with an interval of 21 days. The primary outcome was a change in mean daily total symptom score for runny, itchy, sneezing nose (maximum change, 9.0) or in percentage of well days during the grass pollen season.Treatment with T suis ova (N = 49) compared with placebo (N = 47) caused transient diarrhea peaking at day 41 in 33% of participants (placebo, 2%), and increased eosinophil counts (P.001) and T suis-specific IgE (P.05), IgG (P.001), IgG(4) (P.003), and IgA (P.001), whereas there was no significant change in symptom scores (0.0; 95% CI, -0.5 to 0.4; P = .87), well days (3%; 95% CI, -9% to 14%; P = .63), total histamine (P = .44), grass-specific IgE (P = .76), or diameter of wheal reaction on skin prick testing with grass (P = .85) or 9 other allergens.Repeated treatment with the helminth T suis induced a substantial clinical and immunologic response as evidence of infection, but had no therapeutic effect on allergic rhinitis.