The Genetic Profile and Serum Level of IL-8 Are Associated with Chronic Hepatitis B and C Virus Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population Evaluated
2.2. Genotyping of IL8 A/T (rs4073)
2.3. Laboratory Data
2.4. Histopathological Analysis
2.5. Quantification of Plasma IL-8
2.6. Statistical Analysis
2.7. Plasma Viral Load
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Shin, E.-C.; Sung, P.S.; Park, S.-H. Immune responses and immunopathology in acute and chronic viral hepatitis. Nat. Rev. Immunol. 2016, 16, 509–523. [Google Scholar] [CrossRef]
- Aleman, S.; Rahbin, N.; Weiland, O.; Davidsdottir, L.; Hedenstierna, M.; Rose, N.; Verbaan, H.; Stål, P.; Carlsson, T.; Norrgren, H.; et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin. Infect. Dis. 2013, 57, 230–236. [Google Scholar] [CrossRef]
- Heim, M.H.; Thimme, R. Innate and adaptive immune responses in HCV infections. J. Hepatol. 2014, 61, S14–S25. [Google Scholar] [CrossRef] [Green Version]
- Pellicoro, A.; Ramachandran, P.; Iredale, J.P.; Fallowfield, J. Liver fibrosis and repair: Immune regulation of wound healing in a solid organ. Nat. Rev. Immunol. 2014, 14, 181–194. [Google Scholar] [CrossRef]
- Tanaka, M.; Miyajima, A. Liver regeneration and fibrosis after inflammation. Inflamm. Regen. 2016, 36, 1–6. [Google Scholar] [CrossRef] [Green Version]
- Bedossa, P.; Poynard, T. An Algorithm for the Grading of Activity in Chronic Hepatitis C. Hepatology 1996, 24, 289–293. [Google Scholar] [CrossRef]
- Saile, B.; Ramadori, G. Inflammation, Damage Repair and Liver Fibrosis—Role of Cytokines and Different Cell Types. Z. Für Gastroenterol. 2007, 45, 77–86. [Google Scholar] [CrossRef] [PubMed]
- Harada, A.; Sekido, N.; Akahoshi, T.; Wada, T.; Mukaida, N.; Matsushima, K. Essential involvement of interleukin-8 (IL-8) in acute inflammation. J. Leukoc. Biol. 1994, 56, 559–564. [Google Scholar] [CrossRef] [PubMed]
- Reyes, G.R. The nonstructural NS5A protein of hepatitis C virus: An expanding, multifunctional role in enhancing hepatitis C virus pathogenesis. J. Biomed. Sci. 2002, 9, 187–197. [Google Scholar] [CrossRef] [PubMed]
- Hull, J. Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax 2000, 55, 1023–1027. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Roebuck, K.A. Regulation of Interleukin-8 Gene Expression. J. Interf. Cytokine Res. 1999, 19, 429–438. [Google Scholar] [CrossRef]
- Masumoto, T.; Ohkubo, K.; Yamamoto, K.; Ninomiya, T.; Abe, M.; Akbar, S.M.; Michitaka, K.; Horiike, N.; Onji, M. Serum IL-8 levels and localization of IL-8 in liver from patients with chronic viral hepatitis. Hepatogastroenterology 1998, 45, 1630–1634. [Google Scholar] [PubMed]
- Yang, K.; Guan, S.-H.; Zhang, H.; Pan, Y.; Wu, Y.-Y.; Wang, A.-H.; Sun, B.-B. Enhanced Levels of Interleukin-8 Are Associated with Hepatitis B Virus Infection and Resistance to Interferon-Alpha Therapy. Int. J. Mol. Sci. 2014, 15, 21286–21298. [Google Scholar] [CrossRef] [Green Version]
- Ayres, M.; Ayres Júnior, M.; Ayres, D.L.; Santos, A.S. BioEstat 5.3: Aplicações Estatísticas nas Áreas das Ciências Biológicas e Médicas; Publicações Avulsas do Mamirauá: Belém, Brazil, 2011; p. 364. [Google Scholar]
- Lee, T.C.; Savoldo, B.; Barshes, N.R.; Rooney, C.M.; Heslop, H.E.; Gee, A.P.; Caldwell, Y.; Scott, J.D.; Goss, J.A. Use of cytokine polymorphisms and Epstein-Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients. Clin. Transplant. 2006, 20, 389–393. [Google Scholar] [CrossRef] [PubMed]
- Xu, D.; Li, J.; Huang, X.; Lin, A.; Gai, Z.; Chen, Z. Impact of IL-8-251A/T gene polymorphism on severity of disease caused by enterovirus 71 infection. Arch. Virol. 2016, 161, 203–207. [Google Scholar] [CrossRef] [PubMed]
- Queiroz, M.A.F.; Azevedo, V.N.; Amoras, E.S.G.; Moura, T.C.F.; Ishak, M.O.G.; Ishak, R.; Vallinoto, A.C.R.; Feitosa, R.N.M. IFNG +874A/T Polymorphism Among Asymptomatic HTLV-1-Infected Individuals Is Poten-tially Related to a Worse Prognosis. Front. Microbiol. 2018, 18, 795. [Google Scholar] [CrossRef] [PubMed]
- Qin, X.; Deng, Y.; Liao, X.-C.; Mo, C.-J.; Li, X.; Wu, H.-L.; He, Y.-N.; Huang, X.-M.; Peng, T.; Chen, Z.-P.; et al. The IL-8 Gene Polymorphisms and the Risk of the Hepatitis B Virus/Infected Patients. DNA Cell Biol. 2012, 31, 1125–1130. [Google Scholar] [CrossRef]
- Borekci, G.; Karakas Celik, S.; Kandemir, O.; Aras, N.; Yalin, S. Kronik hepatit B ve C hastalarında IL-1 beta, IL-1 reseptör antagonisti ve IL-8 gen polimorfizmlerinin araştırılması Investigation of IL-1 beta, IL-1 receptor antagonist and IL-8 gene polymorphisms in patients with chronic hepatitis B and C. Mikrobiyol. Bul. 2014, 48, 271–282. [Google Scholar] [CrossRef] [PubMed]
- Santos, N.P.; Ribeiro-Rodrigues, E.M.; Ribeiro-Dos-Santos, A.K.; Pereira, R.; Gusmão, L.; Amorim, A.; Guerreiro, J.F.; Zago, M.A.; Matte, C.; Hutz, M.H.; et al. Assessing individual interethnic admixture and population substructure using a 48-insertion-deletion (INSEL) ancestry-informative marker (AIM) panel. Hum. Mutat. 2009, 31, 184–190. [Google Scholar] [CrossRef] [PubMed]
- Al-Wabel, A.; Al-Knawy, B.; Raziuddin, S. Interleukin-8 and Granulocyte-Macrophage Colony-Stimulating Factor Secretion in Hepatocellular Carcinoma and Viral Chronic Active Hepatitis. Clin. Immunol. Immunopathol. 1995, 74, 231–235. [Google Scholar] [CrossRef]
- Polyak, S.J.; Khabar, K.S.A.; Rezeiq, M.; Gretch, D.R. Elevated Levels of Interleukin-8 in Serum Are Associated with Hepatitis C Virus Infection and Resistance to Interferon Therapy. J. Virol. 2001, 75, 6209–6211. [Google Scholar] [CrossRef] [Green Version]
- Han, Z.Q.; Huang, T.; Deng, Y.Z.; Zhu, G.Z. Expression profile and kinetics of cytokines and chemokines in patients with chronic hepatitis C. Int. J. Clin. Exp. Med. 2015, 8, 17995–18003. [Google Scholar]
- Tian, M.; Zhao, D.Y.; Wen, G.Y.; Shi, S.Y.; Chen, R.H. Association between interleukin-8 gene-251 locus polymorphism and respiratory syncytial virus bronchiolitis and post-bronchiolitis wheezing in infants. Zhonghua Er Ke Za Zhi 2007, 45, 856–859. [Google Scholar]
- Tachibana, Y.; Nakamoto, Y.; Mukaida, N.; Kaneko, S. Intrahepatic interleukin-8 production during disease progression of chronic hepatitis C. Cancer Lett. 2007, 251, 36–42. [Google Scholar] [CrossRef]
- Zimmermann, H.W.; Seidler, S.; Gassler, N.; Nattermann, J.; Luedde, T.; Trautwein, C.; Tacke, F. Interleukin-8 Is Activated in Patients with Chronic Liver Diseases and Associated with Hepatic Macrophage Accumulation in Human Liver Fibrosis. PLoS ONE 2011, 6, e21381. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Gao, Y.; Du, C.; Markowitz, G.J.; Fu, J.; Zhang, Z.; Liu, C.; Qin, W.; Wang, H.; Wang, F.; et al. Hepatitis B–Induced IL8 Promotes Hepatocellular Carcinoma Venous Metastasis and Intrahepatic Treg Accumulation. Cancer Res. 2021, 81, 2386–2398. [Google Scholar] [CrossRef] [PubMed]
- Yu, Y.; Gong, R.; Mu, Y.; Chen, Y.; Zhu, C.; Sun, Z.; Chen, M.; Liu, Y.; Zhu, Y.; Wu, J. Hepatitis B Virus Induces a Novel Inflammation Network Involving Three Inflammatory Factors, IL-29, IL-8, and Cyclooxygenase-2. J. Immunol. 2011, 187, 4844–4860. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koo, B.C.A.; McPoland, P.; Wagoner, J.P.; Kane, O.J.; Lohmann, V.; Polyak, S.J. Relationships between Hepatitis C Virus Replication and CXCL-8 Production In Vitro. J. Virol. 2006, 80, 7885–7893. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Langhans, B.; Krämer, B.; Louis, M.; Nischalke, H.D.; Hüneburg, R.; Staratschek-Jox, A.; Odenthal, M.; Manekeller, S.; Kalff, M.F.J.; Fischer, H.P.; et al. Intrahepatic IL-8 producing Foxp3+CD4+ regulatory T cells and fibrogenesis in chronic hepatitis C. J. Hepatol. 2013, 59, 229–235. [Google Scholar] [CrossRef] [PubMed]
- Larrubia, J.R.; Moreno-Cubero, E.; Lokhande, M.U.; García-Garzón, S.; Lázaro, A.; Miquel, J.; Perna, C.; Sanz-de-Villalobos, E. Adaptive immune response during hepatitis C virus infection. World J. Gastroenterol. 2014, 20, 3418–3430. [Google Scholar] [CrossRef] [PubMed]
- Pollicino, T.; Bellinghieri, L.; Restuccia, A.; Raffa, G.; Musolino, C.; Alibrandi, A.; Teti, D.; Raimondo, G. Hepatitis B virus (HBV) induces the expression of interleukin-8 that in turn reduces HBV sensitivity to interferon-alpha. Virology 2013, 444, 317–328. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dunn, C.; Brunetto, M.; Reynolds, G.; Christophides, T.; Kennedy, P.T.; Lampertico, P.; Das, A.; Borrow, P.; Williams, K.; Humphreys, E.; et al. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J. Exp. Med. 2007, 204, 667–680. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tan, A.T.; Koh, S.; Goh, W.; Zhe, H.Y.; Gehring, A.J.; Lim, S.G.; Bertoletti, A.A. longitudinal analysis of innate and adaptive immune profile during hepatic flares in chronic hepatitis B. J. Hepatol. 2010, 52, 330–339. [Google Scholar] [CrossRef] [PubMed]
- Gehring, A.J.; Koh, S.; Chia, A.; Paramasivam, K.; Chew, V.S.; Ho, Z.Z.; Lee, K.H.; Maini, M.K.; Madhavan, K.; Lim, S.G.; et al. Licensing virus-specific T cells to secrete the neutrophil attracting chemokine CXCL-8 during hepatitis B virus infection. PLoS ONE 2011, 6, e23330. [Google Scholar] [CrossRef] [Green Version]
Variables | HBV (n = 74) | HCV (n = 100) |
---|---|---|
Sex, F/M (%) | 28/46 | 49/51 |
ALT (IU/L), median/IQR | 29/37 | 58/59 |
AST (IU/L), median/IQR | 29/30 | 59/54.5 |
GGT (IU/L), median/IQR | 34.5/38.75 | 67/90.5 |
Viral load (log10), median/IQR | 2.8/1.7 | 5.4/0.7 |
Fibrosis score | ||
0 to 2 | 62 (83.8%) | 69 (69%) |
3 to 4 | 12 (16.2%) | 31 (31%) |
Inflammatory Activity | * | ** |
0 to 1 | 39 (75.4%) | 50 (54.9%) |
2 to 3 | 16 (24.6%) | 41 (45.1%) |
Genotypic and Allelic Profiles | HBV n (%) | HCV n (%) | CG n (%) | p1 | p2 |
---|---|---|---|---|---|
IL8-251 A/T | |||||
AA | 17 (22.97) | 20 (20) | 54 (18) | 0.1971 | 0.9044 |
AT | 41 (55.40) | 49 (49) | 150 (50) | ||
TT | 16 (21.62) | 31 (31) | 96 (32) | ||
A | 0.51 | 0.45 | 0.43 | 0.3212 | 0.8867 |
T | 0.49 | 0.55 | 0.57 |
Genetic Profile | Inflammatory Activity | Fibrosis Score | ||||
---|---|---|---|---|---|---|
0 to 1 | 2 to 3 | p | 0 to 2 | 3 to 4 | p | |
n (%) | n (%) | n (%) | n (%) | |||
IL8-251 A/T | ||||||
HBV | ||||||
AA | 12 (19.7) | 8 (50) | 0.4212 * | 11 (17.7) | 6 (50) | 1.000 * |
AT | 35 (57.4) | 4 (25) | 36 (58.1) | 5 (41.7) | ||
TT | 14 (22.9) | 4 (25) | 15 (24.2) | 1 (8.3) | ||
A | 0.48 | 0.63 | 0.0464 ** | 0.47 | 0.70 | 0.0016 ** |
T | 0.52 | 0.37 | 0.53 | 0.30 | ||
HCV | 0.3724 ** | 0.5135 ** | ||||
AA | 11 (22) | 6 (14.6) | 15 (21.8) | 5 (16.14) | ||
AT | 27 (54) | 20 (48.8) | 35 (50.7) | 14 (45.16) | ||
TT | 12 (24) | 15 (36.6) | 19 (27.5) | 12 (38.7) | ||
A | 0.49 | 0.39 | 0.1998 ** | 0.47 | 0.39 | 0.3174 ** |
T | 0.51 | 0.61 | 0.53 | 0.61 |
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Amoras, E.d.S.G.; de Brito, W.B.; Queiroz, M.A.F.; Conde, S.R.S.d.S.; Cayres Vallinoto, I.M.V.; Ishak, R.; Vallinoto, A.C.R. The Genetic Profile and Serum Level of IL-8 Are Associated with Chronic Hepatitis B and C Virus Infection. Biomolecules 2021, 11, 1664. https://doi.org/10.3390/biom11111664
Amoras EdSG, de Brito WB, Queiroz MAF, Conde SRSdS, Cayres Vallinoto IMV, Ishak R, Vallinoto ACR. The Genetic Profile and Serum Level of IL-8 Are Associated with Chronic Hepatitis B and C Virus Infection. Biomolecules. 2021; 11(11):1664. https://doi.org/10.3390/biom11111664
Chicago/Turabian StyleAmoras, Ednelza da Silva Graça, William Botelho de Brito, Maria Alice Freitas Queiroz, Simone Regina Souza da Silva Conde, Izaura Maria Vieira Cayres Vallinoto, Ricardo Ishak, and Antonio Carlos Rosário Vallinoto. 2021. "The Genetic Profile and Serum Level of IL-8 Are Associated with Chronic Hepatitis B and C Virus Infection" Biomolecules 11, no. 11: 1664. https://doi.org/10.3390/biom11111664