Helminth Infection Enhances Disease in a Murine TH2 Model of Colitis

Background & Aims: There is convincing evidence from animal and human studies that infection with parasitic helminths can alleviate the histopathology and symptoms of colitis. Here the ability of the rat tapeworm Hymenolepis diminuta to affect the course of oxazolone-induced colitis (a TH2 model) was assessed. Methods: Mice were infected with H diminuta and 8 days later they received oxazolone (3 mg in 50% EtOH, intrarectal). On autopsy (3 or 7 days postoxazolone), disease severity was assessed by macroscopic clinical scores, histologic damage scores, myeloperoxidase and eosinophil peroxidase activity, and cytokine synthesis. Results: As gauged by all markers of gut function, infection with H diminuta caused a significant exacerbation of oxazolone-induced colitis. Indeed, while mice receiving oxazolone only began to recover ∼3–4 days posttreatment, the cotreated group continued to deteriorate. Helminth infection, independent of oxazolone administration, enhanced IL-4, IL-5, IL-10, and IL-13 production from in vitro stimulated immune cells and evoked increases in colonic eosinophil peroxidase of cotreated mice. Finally, while knockout of natural killer (NK) and NK-T cells by administration of a neutralizing NK1.1 antibody reduced the inflammation in oxazolone and oxazolone + H diminuta-treated animals, mice in the latter group still displayed significant colitis. Conclusions: We have shown that H diminuta infection is beneficial in other models of colitis. The current data is presented as a caveat to the position that parasitic helminths in general can be considered as a therapy for heterogeneous inflammatory disorders without careful analysis of the immunologic basis of the condition.

Abbreviations used in this paper: AB, antibodies, AMT, 3-amino-1,2,4-triazole, ELISA, enzyme-linked immunosorbent assay, EPO, eosinophil peroxidase, IBD, inflammatory bowel disease, IL, interleukin, IR, intrarectal, MLNs, mesenteric lymph nodes, MPO, myeloperoxidase, NK, natural killer, RT-PCR, reverse transcriptase polymerase chain reaction, SEM, standard error of the mean, TGFβ, transforming growth factor, TH, T helper, TNFα, tumor necrosis factor alpha