Exacerbation of Oxazolone Colitis by Infection with the Helminth Hymenolepis diminuta Involvement of IL-5 and Eosinophils

Substantial data show that infection with helminth parasites ameliorates colitis however oxazolone induced colitis is exaggerated m mice infected with the tapeworm Hymenolepis diminuta We tested the hypothesis that the IL 5 response to helminth infection enhances the seventy of oxazolone induced colitis Mice were infected with H diminuta and 8 days later were treated with oxazolone +/- anti-IL 5 antibodies Colitis was assessed 72 hours postoxazolone treatment by disease activity scores myeloperoxidase activity and histopathology Other mice received injections of a replication deficient adenovirus that carried the IL 5 (Ad IL 5) gene or a control adeno virus (Ad delete) +/- oxazolone The effect of H diminuta + oxazolone in CCL11/CCL22 (eotaxin 1 and 2) knockout (KO) mice was determined Helminth infection and Ad IL 5 treatment increased H. 5 and eosinophil numbers In vivo neutralization of IL 5 significantly reduced the severity of colitis in H diminuta + oxazolone treated mice and H diminuta did not exaggerate oxazolone induced colitis in CCL11/CCL22 KO mice Mice receiving Ad IL 5 only had no colitis while oxazolone induced colitis was more severe in animals cotreated with Ad IL 5 (Ad delete + oxazolone was not significantly different from oxazolone only) Thus while there is much to be gleaned about antiinflammatory mechanisms from rodent helminth model systems, these data illustrate the caveat that infection with helminth parasites as a therapy could be contraindicated m patients with eosinophilia or elevated IL 5 unless coupled to appropriate measures to block IL 5 and/or eosinophil activity (Am J Pathol 2010 177 2850-2859 DOI 10 2353/ajpath 2010 100537)