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Title
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Critical role of interleukin 5 and eosinophils in concanavalin A-induced hepatitis in mice
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Author
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Abstract
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| Background & Aims: Eosinophils are observed in several liver diseases, but their contribution in the pathogenesis of these disorders remains poorly investigated. Concanavalin A (Con A)-induced hepatitis is an experimental model of immune-mediated liver injury in which natural killer T (NKT) cells play a critical role through the production of interleukin (IL)-4 and the expression of Fas ligand (FasL). Because activated NKT cells also produce IL-5, a critical cytokine for eosinophil maturation and function, the role of IL-5 was investigated in this model. Methods: IL-5-deficient mice, eosinophil depletion in wild-type (WT) mice, and NKT cell transfer from WT- or IL-5-deficient mice into NKT cell-deficient mice were used to assess the role of IL-5 and eosinophils. Results: Liver eosinophil infiltrate and IL-5 production were observed after Con A challenge. Liver injury was dramatically reduced in IL-5-deficient or eosinophil-depleted mice. In addition, residual hepatitis observed in Fas-deficient mice was abolished after IL-5 neutralization. Finally, we showed that NKT cells constituted a critical source of IL-5. Indeed, transfer of WT NKT cells to mice lacking NKT cells restored liver injury, whereas transfer of IL-5-deficient NKT cells did not. Conclusions: These observations highlight the pathologic role of IL-5 and eosinophils in experimental immune-mediated hepatitis. |
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Language
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English
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Source (journal)
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Gastroenterology. - Baltimore, Md
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Publication
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Baltimore, Md
:
2002
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ISSN
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0016-5085
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DOI
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10.1053/GAST.2002.33620
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Volume/pages
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122
:7
(2002)
, p. 2001-2010
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ISI
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000176280300032
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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