IL‐17 neutralization significantly ameliorates hepatic granulomatous inflammation and liver damage in Schistosoma japonicum infected mice

• Published in: European journal of immunology 2012-06, Vol.42 (6), p.1523-1535
• Main Authors: Zhang, Yuxia, Chen, Liuxi, Gao, Wenda, Hou, Xin, Gu, Yuqing, Gui, Li, Huang, Dake, Liu, Miao, Ren, Cuiping, Wang, Siying, Shen, Jijia
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; CD4+ T cells; Chemokines; Chemokines - biosynthesis; Cytokines; Cytokines - biosynthesis; Female; Granuloma - drug therapy; Granuloma - etiology; Granulomatous inflammation; IL‐17; Immune system; Inflammation - drug therapy; Inflammation - etiology; Inflammation Mediators - metabolism; Interleukin-17 - physiology; Liver Diseases - drug therapy; Liver Diseases - etiology; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Rodents; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis japonica - complications; Schistosomiasis japonica - drug therapy; Schistosomiasis japonica - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201141933

IL‐17 is a signature cytokine of Th17 cells implicated in the induction and progression of chronic inflammatory diseases. Several studies in C57BL/6 mice, immunized with soluble schistosome egg Ags (SEA) in complete Freund's adjuvant (CFA), and subsequently infected with Schistosoma mansoni (S. mansoni) have shown that severe hepatic granulomatous inflammation is correlated with high levels of IL‐17. Here, using a Schistosoma japonicum (S. japonicum) larvae infection model in C57BL/6 mice, we analyzed the dynamic expression of IL‐17 in infected livers by RT‐qPCR and ELISA. Our results showed that IL‐17 expression was elevated during the course of infection. The temporal expression of IL‐17 and cytokines/chemokines involved in the induction and effector function of Th17 cells was paralleled with hepatic granulomatous inflammation. Treatment of S. japonicum infected mice with IL‐17‐neutralizing mAb resulted in significant downmodulation of granulomatous inflammation and hepatocyte necrosis. The protection was associated with lower expression of proinflammatory cytokines/chemokines, such as IL‐6, IL‐1β, CXCL1, and CXCL2 and a reduced number of infiltrating neutrophils. Anti‐IL‐17 mAb significantly ameliorated hepatic granulomatous inflammation, partly through the downregulation of proinflammatory cytokines/chemokines and recruitment of neutrophils. Our data indicate a pathogenic role of Th17/IL‐17 in hepatic immunopathology in S. japonicum infected mice.