Fallon P G, Richardson E J, McKenzie G J, McKenzie A N
Department of Pathology, University of Cambridge, Cambridge, United Kingdom; and Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
J Immunol. 2000 Mar 1;164(5):2585-91. doi: 10.4049/jimmunol.164.5.2585.
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.
对小鼠进行曼氏血吸虫感染实验会引发一种由2型细胞因子介导的动态病理过程。我们使用白细胞介素-4（IL-4）缺陷型、白细胞介素-13（IL-13）缺陷型和IL-4/13双缺陷型小鼠，来剖析这些细胞因子在曼氏血吸虫感染后免疫反应和病理发展过程中的作用。我们证明，虽然这两种细胞因子对于产生强大的由辅助性T细胞2（Th2）驱动、富含嗜酸性粒细胞的肉芽肿反应都是必需的，但它们也发挥着不同的功能，这为治疗干预确定了新的靶点。IL-13缺陷型小鼠在感染后显示出显著提高的存活率，这与肝纤维化减轻相关。相比之下，IL-4缺陷型和IL-4/13双缺陷型小鼠的死亡率增加，这与肝细胞损伤和肠道病理变化相关。因此，我们证明，在动态的2型细胞因子疾病过程中，IL-13对感染后的生存有害，而IL-4则有益。
