Critical role of interleukin 5 and eosinophils in concanavalin A-induced hepatitis in mice.
OBJECTIVE
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.
Louis
Hubert
H
Laboratory of Experimental Gastroenterology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. hlouis@ulb.ac.be
Le Moine
Alain
A
Flamand
Véronique
V
Nagy
Nathalie
N
Quertinmont
Eric
E
Paulart
Frédéric
F
Abramowicz
Daniel
D
Le Moine
Olivier
O
Goldman
Michel
M
Devière
Jacques
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000503:physiopathology*; D003208:Concanavalin A; D004804:Eosinophils / Q000502:physiology*; D015848:Interleukin-5 / Q000276:immunology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019014:fas Receptor / Q000235:genetics / Q000502:physiology
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D019014:fas Receptor; D003208:Concanavalin A