Treatment with interleukin-18 binding protein ameliorates Toxoplasma gondii-induced small intestinal pathology that is induced by bone marrow cell-derived interleukin-18
| Autor: | U. Steinhoff, S. Enders, Markus M. Heimesaat, Daniela Struck, A. Stallmach, Oliver Liesenfeld, C. Schmidt, I. Frank |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Lamina propria
Pathology medicine.medical_specialty Necrosis Stromal cell Intestinal parasite Toxoplasma gondii Biology medicine.disease medicine.disease_cause biology.organism_classification medicine.anatomical_structure Immunopathology medicine Ileitis Interleukin 18 Original Article medicine.symptom |
| Popis: | Peroral infection with Toxoplasma gondii results in a Th1-type immunopathology characterized by small intestinal necrosis and is dependent on IL-18. In the present study, we investigated whether treatment with IL-18 binding protein (IL-18bp) prevents ileal pathology. We observed increased expression of IL-18bp in intestinal biopsies of mice following infection. Whereas small intestines of control mice showed severe necrosis with complete destruction of the small intestinal architecture, mice treated with IL-18bp daily displayed only mild inflammatory changes including flattening of villi and edema in the space between the epithelium and lamina propria. Small intestinal parasite loads and concentrations of pro-inflammatory cytokines did not differ in control and IL-18bp-treated mice. Binding of IL-18 to immobilized IL-18bp revealed a remarkably slow dissociation rate, indicating high affinity. Using chimeric mice we observed that bone marrow-derived rather than stromal cells were the primary source of IL-18 that resulted in small intestinal pathology following peroral infection with T. gondii. In conclusion, the results presented here suggest that IL-18bp may be an effective and safe treatment for small intestinal inflammation. Antigen-presenting rather than epithelial cells appear to be the main source of IL-18 in T. gondii-induced small intestinal inflammation. |
| Databáze: | OpenAIRE |
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