Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent.
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.
Fallon
P G
PG
Department of Pathology, University of Cambridge, Cambridge, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom. pgf20@cam.ac.uk
Richardson
E J
EJ
McKenzie
G J
GJ
McKenzie
A N
AN
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004803:Eosinophilic Granuloma / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018793:Interleukin-13 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007411:Intestinal Diseases, Parasitic / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000276:immunology* / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012555:Schistosomiasis mansoni / Q000209:etiology / Q000276:immunology* / Q000401:mortality / Q000473:pathology*
D016207:Cytokines; D018793:Interleukin-13; D015847:Interleukin-4