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The Journal of Immunology, 2000, 164: 2585-2591.
Copyright © 2000 by The American Association of Immunologists

Schistosome Infection of Transgenic Mice Defines Distinct and Contrasting Pathogenic Roles for IL-4 and IL-13: IL-13 Is a Profibrotic Agent1

Padraic G. Fallon2,*, Emma J. Richardson*, Grahame J. McKenzie{dagger} and Andrew N. J. McKenzie{dagger}

* Department of Pathology, University of Cambridge, Cambridge, United Kingdom; and {dagger} Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom

Experimental Schistosoma mansoni infections of mice lead to a dynamic type 2 cytokine-mediated pathological process. We have used IL-4-deficient, IL-13-deficient, and IL-4/13-deficient mice to dissect the role of these cytokines in the development of immune response and pathology following S. mansoni infection. We demonstrate that while both of these cytokines are necessary to develop a robust Th2 cell-driven, eosinophil-rich granuloma response, they also perform disparate functions that identify novel sites for therapeutic intervention. IL-13-deficient mice demonstrated significantly enhanced survival following infection, which correlated with reduced hepatic fibrosis. In contrast, increased mortality was manifest in IL-4-deficient and IL-4/13-deficient mice, and this correlated with hepatocyte damage and intestinal pathology. Therefore, we demonstrate that during a dynamic type 2 cytokine disease process IL-13 is detrimental to survival following infection, whereas IL-4 is beneficial.




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 Infect. Immun.Home page
E. A. Patton, L. R. Brunet, A. C. La Flamme, J. Pedras-Vasconcelos, M. Kopf, and E. J. Pearce
Severe Schistosomiasis in the Absence of Interleukin-4 (IL-4) Is IL-12 Independent
Infect. Immun., January 1, 2001; 69(1): 589 - 592.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A. K. Kacha, F. Fallarino, M. A. Markiewicz, and T. F. Gajewski
Spontaneous Rejection of Poorly Immunogenic P1.HTR Tumors by Stat6-Deficient Mice
J. Immunol., December 1, 2000; 165(11): 6024 - 6028.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
P. G. Fallon, P. Smith, E. J. Richardson, F. J. Jones, H. C. Faulkner, J. Van Snick, J.-C. Renauld, R. K. Grencis, and D. W. Dunne
Expression of Interleukin-9 Leads to Th2 Cytokine-Dominated Responses and Fatal Enteropathy in Mice with Chronic Schistosoma mansoni Infections
Infect. Immun., October 1, 2000; 68(10): 6005 - 6011.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
L. I. Rutitzky, H. J. Hernandez, and M. J. Stadecker
Th1-polarizing immunization with egg antigens correlates with severe exacerbation of immunopathology and death in schistosome infection
PNAS, November 6, 2001; 98(23): 13243 - 13248.
[Abstract] [Full Text] [PDF]


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