Table 1.
Helminth-based therapeutic studies
| Organism | Disease | Treatment | Description of effects | Reference |
|---|---|---|---|---|
| Mouse | OVA-alum and Der p1-alum (HDM allergen)-driven models of allergic airway inflammation | H. polygyrus larvae | H. polygyrus-infected mice had reduced airway cellular infiltrates (including reduced eosinophilia and neutrophilia), reduced lung type 2 cytokines, and reduced lung histopathology | 26 |
| Mouse | OVA-alum-driven model of allergic airway inflammation | H. polygyrus larvae | H. polygyrus-infected mice had reduced airway eosinophilia, reduced bronchial hyperreactivity, and reduced allergen-specific Th2 responses | 27 |
| Mouse | OVA-alum-driven model of allergic airway inflammation | HES | HES given at allergen sensitization or challenge reduced airway cellular infiltrates and lung eosinophilia | 110 |
| Mouse | Alternaria alternata-driven model of allergic airway inflammation | HES | HES blocked lung eosinophilia, IL-33 release, and innate lymphoid cell type 2 cytokine production | 111 |
| Mouse | TNBS-induced colitis | Schistosoma mansoni- or Ancylostoma caninum-soluble proteins | Intraperitoneal helminth protein administration reduced macroscopic inflammation scores and reduced proinflammatory cytokine release (IL-17 and IFN-γ) | 112 |
| Mouse | Systemic–fatal anaphylaxis | S. mansoni cercariae | S. mansoni-infected mice were protected from anaphylaxis | 28 |
| Mouse | T1D (spontaneous development in NOD mice) | H. polygyrus larvae | H. polygyrus infection delayed disease onset | 29,30 |
| Mouse | T1D (spontaneous development in NOD mice) | Litomosoides sigmodontis larvae | L. sigmodontis infection prevented disease onset | 31,32 |
| Mouse | OVA-alum-driven model of allergic airway inflammation and DSS-induced colitis | Recombinant cysteine protease inhibitor (cystatin) of Acanthocheilonema viteae | A. viteae cystatin treatment during OVA sensitization or prior to OVA challenge reduced airway BALF cell counts, airway eosinophilia, bronchial hyperreactivity, and lung histopathology. In the DSS–colitis model, intrarectal A. viteae cystatin resulted in significant reductions in colonic inflammatory index compared to control animals | 114 |
| Mouse | DSS-induced colitis | Ancylostoma ceylanicum crude extract or ES products | Helminth-product-treated mice had reduced clinical and colonic microscopic inflammation scores compared to control mice | 113 |
| Mouse | T1D (spontaneous development in NOD mice) | S. mansoni infection, or treatment with soluble worm or egg extracts | Exposure to worm or egg extract prevented disease onset if given before 4 weeks of age | 116 |
| Mouse | DSS-induced colitis | ES products from A. caninum | Exposure to helminth products reduced intestinal proinflammatory cytokine expression | 115 |
| Humans | CD and UC | Live Trichuris suis eggs | Three out of four CD patients entered remission; fourth patient had a reduction in symptoms. UC patients had a reduction in clinical colitis activity index | 106 |
| Humans | CD | Live T. suis ova | 79.3% of patients had a reduction in CD activity index or remitted | 103 |
| Humans | CD | Live T. suis ova | All doses tested were well tolerated and did not result in treatment-related side effects. Efficacy of a reduction in disease severity not assessed | 104 |
| Humans | UC | Live T. suis ova | A reduction in disease activity was seen in helminth- infected patients compared to placebo group, although this did not reach statistical significance | 108 |
| Humans | CD | Necator americanus larvae | IBD questionnaire results were improved, and cumulative CD activity index scores were decreased | 105 |
| Humans | Allergic rhinoconjunctivitis | N. americanus larvae | Infection well tolerated; no significant differences in allergic symptoms between groups given placebo or N. americanus larvae | 107 |
Abbreviations: OVA, ovalbumin; alum, potassium aluminum sulfate; ES, excretory/secretory; HES, H. polygyrus excretory/secretory product; HDM, house dust mite; BALF, bronchoalveolar lavage fluid; IL, interleukin; IFN, interferon; DSS, dextran sulfate sodium; TNBS, 2,4,6-trinitrobenzene sulfonic acid; T1D, type 1 diabetes; NOD, non-obese diabetic; CD, Crohn’s disease; UC, ulcerative colitis; IBD, inflammatory bowel disease; Th, T-helper.