Skip to main content
Top
Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2016 | Research article

Relevance of serum interleukin-33 and ST2 levels and the natural course of chronic hepatitis B virus infection

Authors: Shu-Ling Huan, Ji-Guang Zhao, Zhen-Li Wang, Shuai Gao, Kai Wang

Published in: BMC Infectious Diseases | Issue 1/2016

Login to get access

Abstract

Background

Interleukin-33 (IL-33) and ST2 have been demonstrated to be associated with liver damage. However, their potential value in hepatitis B virus (HBV) infection remains unknown. This study was designed to investigate the change of serum IL-33 and ST2 levels in the natural course of chronic HBV infection.

Methods

A total of 120 patients with chronic hepatitis B (CHB), 20 chronic hepatitis B virus carriers in immunotolerant phase and 28 healthy controls were enrolled in this study. All patients with CHB were divided into four groups according to their serum ALT levels. The serum levels of IL-33 and ST2 of all participants were determined by enzyme-linked immunosorbent assay, and compared between each two out of those six groups.

Results

No significant differences were found in serum levels of IL-33 and ST2 between the group of CHB with ALT 1–2 upper limit of normal and the healthy controls (P = 0.354 for IL-33 and P = 0.815 for ST2). Other than that, there were significant differences when serum levels of IL-33 and ST2 were compared between any other two out of those six groups (P < 0.05, respectively). The overall correlation analysis indicated that changes of serum IL-33 and ST2 levels were positively associated with ALT levels in patients with chronic HBV infection (rs = 0.879, P < 0.001 for IL-33 and rs = 0.923, P < 0.001 for ST2). No significant differences were found when the serum levels of ALT, IL-33 and ST2 were compared between patients with HBeAg-positive CHB and HBeAg-negative CHB.

Conclusions

Our study revealed that the serum levels of IL-33 and ST2 varied in different courses of chronic hepatitis B virus infection. The serum levels of IL-33 and ST2 elevated as serum ALT levels increased in patients with CHB. They might indicate liver damage for patients with CHB, just like ALT.
Literature
1.
go back to reference Roth GA, Zimmermann M, Lubsczyk BA, et al. Up-regulation of interleukin 33 and soluble ST2 serum levels in liver failure. J Surg Res. 2010;163:e79–83.CrossRefPubMed Roth GA, Zimmermann M, Lubsczyk BA, et al. Up-regulation of interleukin 33 and soluble ST2 serum levels in liver failure. J Surg Res. 2010;163:e79–83.CrossRefPubMed
2.
go back to reference Chen J, Yuan Z. Interplay between hepatitis B virus and the innate immune responses: implications for new therapeutic strategies. Virol Sin. 2014;29:17–24.CrossRefPubMed Chen J, Yuan Z. Interplay between hepatitis B virus and the innate immune responses: implications for new therapeutic strategies. Virol Sin. 2014;29:17–24.CrossRefPubMed
3.
go back to reference Crockett SD, Keeffe EB. Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection. Ann Clin Microbiol Antimicrob. 2005;4:13.CrossRefPubMedPubMedCentral Crockett SD, Keeffe EB. Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection. Ann Clin Microbiol Antimicrob. 2005;4:13.CrossRefPubMedPubMedCentral
4.
go back to reference Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5:215–29.CrossRefPubMed Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5:215–29.CrossRefPubMed
5.
go back to reference Rehermann B. Interaction between the hepatitis C virus and the immune system. Semin Liver Dis. 2000;20:127–41.CrossRefPubMed Rehermann B. Interaction between the hepatitis C virus and the immune system. Semin Liver Dis. 2000;20:127–41.CrossRefPubMed
6.
go back to reference Gonzalez MI, Rubinstein N, Ilarregui JM, Toscano MA, Sanjuan NA, Rabinovich GA. Regulated expression of galectin-1 after in vitro productive infection with herpes simplex virus type 1: implications for T cell apoptosis. Int J Immunopathol Pharmacol. 2005;18:615–23.CrossRefPubMed Gonzalez MI, Rubinstein N, Ilarregui JM, Toscano MA, Sanjuan NA, Rabinovich GA. Regulated expression of galectin-1 after in vitro productive infection with herpes simplex virus type 1: implications for T cell apoptosis. Int J Immunopathol Pharmacol. 2005;18:615–23.CrossRefPubMed
7.
go back to reference Martini F, Agrati C, D'Offizi G, Poccia F. HLA-E up-regulation induced by HIV infection may directly contribute to CD94-mediated impairment of NK cells. Int J Immunopathol Pharmacol. 2005;18:269–76.CrossRefPubMed Martini F, Agrati C, D'Offizi G, Poccia F. HLA-E up-regulation induced by HIV infection may directly contribute to CD94-mediated impairment of NK cells. Int J Immunopathol Pharmacol. 2005;18:269–76.CrossRefPubMed
8.
go back to reference Falasca K, Ucciferri C, Dalessandro M, et al. Cytokine patterns correlate with liver damage in patients with chronic hepatitis B and C. Ann Clin Lab Sci. 2006;36:144–50.PubMed Falasca K, Ucciferri C, Dalessandro M, et al. Cytokine patterns correlate with liver damage in patients with chronic hepatitis B and C. Ann Clin Lab Sci. 2006;36:144–50.PubMed
9.
go back to reference Grzegorzewska AE, Wobszal P, Jagodzinski PP. Interleukin-18 promoter polymorphism and development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients. Kidney Blood Press Res. 2012;35:1–8.CrossRefPubMed Grzegorzewska AE, Wobszal P, Jagodzinski PP. Interleukin-18 promoter polymorphism and development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients. Kidney Blood Press Res. 2012;35:1–8.CrossRefPubMed
10.
go back to reference Wang J, Cai Y, Ji H, et al. Serum IL-33 levels are associated with liver damage in patients with chronic hepatitis B. J Interferon Cytokine Res. 2012;32:248–53.CrossRefPubMedPubMedCentral Wang J, Cai Y, Ji H, et al. Serum IL-33 levels are associated with liver damage in patients with chronic hepatitis B. J Interferon Cytokine Res. 2012;32:248–53.CrossRefPubMedPubMedCentral
11.
go back to reference Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut. 2012;61:1754–64.CrossRefPubMed Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut. 2012;61:1754–64.CrossRefPubMed
12.
go back to reference Chang J, Block TM, Guo JT. The innate immune response to hepatitis B virus infection: implications for pathogenesis and therapy. Antiviral Res. 2012;96:405–13.CrossRefPubMed Chang J, Block TM, Guo JT. The innate immune response to hepatitis B virus infection: implications for pathogenesis and therapy. Antiviral Res. 2012;96:405–13.CrossRefPubMed
13.
go back to reference Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology. 2006;43:S173–81.CrossRefPubMed Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology. 2006;43:S173–81.CrossRefPubMed
14.
go back to reference Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.CrossRefPubMed Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.CrossRefPubMed
15.
go back to reference Jiang Y, Ma Z, Xin G, et al. Th1 and Th2 immune response in chronic hepatitis B patients during a long-term treatment with adefovir dipivoxil. Mediators Inflamm. 2010;2010:143026.PubMedPubMedCentral Jiang Y, Ma Z, Xin G, et al. Th1 and Th2 immune response in chronic hepatitis B patients during a long-term treatment with adefovir dipivoxil. Mediators Inflamm. 2010;2010:143026.PubMedPubMedCentral
16.
go back to reference Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One. 2008;3, e3331.CrossRefPubMedPubMedCentral Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One. 2008;3, e3331.CrossRefPubMedPubMedCentral
17.
go back to reference Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–90.CrossRefPubMed Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–90.CrossRefPubMed
18.
go back to reference Brunner M, Krenn C, Roth G, et al. Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma. Intensive Care Med. 2004;30:1468–73.CrossRefPubMed Brunner M, Krenn C, Roth G, et al. Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma. Intensive Care Med. 2004;30:1468–73.CrossRefPubMed
19.
go back to reference Becerra A, Warke RV, de Bosch N, Rothman AL, Bosch I. Elevated levels of soluble ST2 protein in dengue virus infected patients. Cytokine. 2008;41:114–20.CrossRefPubMedPubMedCentral Becerra A, Warke RV, de Bosch N, Rothman AL, Bosch I. Elevated levels of soluble ST2 protein in dengue virus infected patients. Cytokine. 2008;41:114–20.CrossRefPubMedPubMedCentral
20.
go back to reference Kumar S, Tzimas MN, Griswold DE, Young PR. Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. Biochem Biophys Res Commun. 1997;235:474–8.CrossRefPubMed Kumar S, Tzimas MN, Griswold DE, Young PR. Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. Biochem Biophys Res Commun. 1997;235:474–8.CrossRefPubMed
21.
go back to reference Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y. ST2 protein induced by inflammatory stimuli can modulate acute lung inflammation. Biochem Biophys Res Commun. 2002;299:18–24.CrossRefPubMed Oshikawa K, Yanagisawa K, Tominaga S, Sugiyama Y. ST2 protein induced by inflammatory stimuli can modulate acute lung inflammation. Biochem Biophys Res Commun. 2002;299:18–24.CrossRefPubMed
22.
go back to reference Leung BP, Xu D, Culshaw S, McInnes IB, Liew FY. A novel therapy of murine collagen-induced arthritis with soluble T1/ST2. J Immunol. 2004;173:145–50.CrossRefPubMed Leung BP, Xu D, Culshaw S, McInnes IB, Liew FY. A novel therapy of murine collagen-induced arthritis with soluble T1/ST2. J Immunol. 2004;173:145–50.CrossRefPubMed
23.
go back to reference Cacopardo B, Rita Pinzone M, Palermo F, Nunnari G. Changes in serum Interleukin-33 concentration before and after treatment with pegylated interferon alfa-2a plus ribavirin in patients with chronic hepatitis C genotype 1b infection. Hepat Mon. 2012;12, e7611.CrossRefPubMedPubMedCentral Cacopardo B, Rita Pinzone M, Palermo F, Nunnari G. Changes in serum Interleukin-33 concentration before and after treatment with pegylated interferon alfa-2a plus ribavirin in patients with chronic hepatitis C genotype 1b infection. Hepat Mon. 2012;12, e7611.CrossRefPubMedPubMedCentral
24.
go back to reference Wang J, Zhao P, Guo H, et al. Serum IL-33 levels are associated with liver damage in patients with chronic hepatitis C. Mediators Inflamm. 2012;2012:819636.PubMedPubMedCentral Wang J, Zhao P, Guo H, et al. Serum IL-33 levels are associated with liver damage in patients with chronic hepatitis C. Mediators Inflamm. 2012;2012:819636.PubMedPubMedCentral
25.
go back to reference Arshad MI, Rauch M, L'Helgoualc'h A, et al. NKT cells are required to induce high IL-33 expression in hepatocytes during ConA-induced acute hepatitis. Eur J Immunol. 2011;41:2341–8.CrossRefPubMed Arshad MI, Rauch M, L'Helgoualc'h A, et al. NKT cells are required to induce high IL-33 expression in hepatocytes during ConA-induced acute hepatitis. Eur J Immunol. 2011;41:2341–8.CrossRefPubMed
26.
go back to reference Volarevic V, Mitrovic M, Milovanovic M, et al. Protective role of IL-33/ST2 axis in Con A-induced hepatitis. J Hepatol. 2012;56:26–33.CrossRefPubMed Volarevic V, Mitrovic M, Milovanovic M, et al. Protective role of IL-33/ST2 axis in Con A-induced hepatitis. J Hepatol. 2012;56:26–33.CrossRefPubMed
27.
go back to reference Marvie P, Lisbonne M, L'Helgoualc'h A, et al. Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med. 2010;14:1726–39.CrossRefPubMed Marvie P, Lisbonne M, L'Helgoualc'h A, et al. Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med. 2010;14:1726–39.CrossRefPubMed
28.
go back to reference Rank MA, Kobayashi T, Kozaki H, Bartemes KR, Squillace DL, Kita H. IL-33-activated dendritic cells induce an atypical TH2-type response. J Allergy Clin Immunol. 2009;123:1047–54.CrossRefPubMedPubMedCentral Rank MA, Kobayashi T, Kozaki H, Bartemes KR, Squillace DL, Kita H. IL-33-activated dendritic cells induce an atypical TH2-type response. J Allergy Clin Immunol. 2009;123:1047–54.CrossRefPubMedPubMedCentral
Metadata
Title
Relevance of serum interleukin-33 and ST2 levels and the natural course of chronic hepatitis B virus infection
Authors
Shu-Ling Huan
Ji-Guang Zhao
Zhen-Li Wang
Shuai Gao
Kai Wang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1543-x

Other articles of this Issue 1/2016

BMC Infectious Diseases 1/2016 Go to the issue