Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis

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 muri...

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Main Authors: Ma Liang, Zhang Liwen, Zhuang Yun, Ding Yanbo, Chen Jianping
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/7964654
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author Ma Liang
Zhang Liwen
Zhuang Yun
Ding Yanbo
Chen Jianping
author_facet Ma Liang
Zhang Liwen
Zhuang Yun
Ding Yanbo
Chen Jianping
author_sort Ma Liang
collection DOAJ
description 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-γ, TNF-α), 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 (γ-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-γ). 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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spelling doaj-art-bf8cc2850a4a4ff088a1e5e32da494182025-02-03T05:44:27ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/79646547964654Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune HepatitisMa Liang0Zhang Liwen1Zhuang Yun2Ding Yanbo3Chen Jianping4Department of Digestive Disease, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaDepartment of Pediatrics, The Second People’s Hospital of Changzhou, Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, ChinaDepartment of Digestive Disease, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaDepartment of Digestive Disease, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaDepartment of Digestive Disease, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, ChinaThis 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-γ, TNF-α), 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 (γ-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-γ). 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.http://dx.doi.org/10.1155/2018/7964654
spellingShingle Ma Liang
Zhang Liwen
Zhuang Yun
Ding Yanbo
Chen Jianping
Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis
Mediators of Inflammation
title Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis
title_full Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis
title_fullStr Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis
title_full_unstemmed Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis
title_short Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis
title_sort serum levels of il 33 and correlation with il 4 il 17a and hypergammaglobulinemia in patients with autoimmune hepatitis
url http://dx.doi.org/10.1155/2018/7964654
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