Journal
MEDIATORS OF INFLAMMATION
Volume 2018, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2018/7964654
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Funding
- National Natural Science Foundation of China [81700500]
- Applied Basic Research Programs of Science, Technology Department of Changzhou City [CJ20160031]
- Research Project of Jiangsu Province Commission of Health and Family Planning [H201547]
- Major Scientific and Technological Project of Changzhou City Commission of Health and Family Planning [ZD201612]
- Scientific and Technological Project of Nanjing Medical University [2017NJMU042]
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This study investigated the role of IL-33 in the pathogenesis of autoimmune hepatitis (AIH). The levels of IL-33/sST2 and Th1/Th2/ Th17-type cytokines were determined by enzyme-linked immunosorbent assay in serum samples obtained from 30 AIH patients and 20 healthy controls (HCs). In addition, a murine model of experimental AIH (EAIH) was established to investigate the role of IL-33 in disease progression. The serum levels of IL-33, sST2, Th17 cytokines (IL-17A), Th1 cytokines (IFN-gamma, TNF-alpha), and Th2 cytokines (IL-4) were significantly elevated in AIH patients compared to HCs. Following immunosuppression therapy, serum levels of IL-33 and sST2 were significantly decreased. Additionally, the serum levels of IL-33 in AIH patients were correlated positively with markers of hypergammaglobulinemia (IgG, IgM, and IgA) and liver injury (gamma-GT/ALP). Also, the serum levels of IL-33 in AIH patients were correlated positively with proinflammatory cytokine levels (IL-17A and IL-4). Interestingly, treatment of EAIH mice with a specific IL-33 neutralizing antibody significantly reversed the increasing trend in serum ALT/AST and inhibited the production of the type 2 (IL-4) and type 17 cytokines (IL-17) but not the type 1 cytokine (IFN-gamma). Our findings highlight the possible role of the IL-33/sST2 axis in the progression of AIH, opening a new door for developing a novel therapeutic strategy for AIH.
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