Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and 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-1 3-deficient, and IL-4/13-deficient mice to dissect the role of these cytoki nes in the development of immune response and pathology following S, manson i infection. We demonstrate that while both of these cytokines are necessar y to develop a robust Th2 cell-driven, eosinophil-rich granuloma response, they also perform disparate functions that identify novel sites for therape utic intervention. IL-13-deficient mice demonstrated significantly enhanced survival following infection, which correlated with reduced hepatic fibros is. In contrast, increased mortality was manifest in IL-4-deficient and IL- 4/13-deficient mice, and this correlated with hepatocyte damage and intesti nal pathology, Therefore, we demonstrate that during a dynamic type 2 cytok ine disease process IL-13 is detrimental to survival following infection, w hereas IL-4 is beneficial.