Interleukin-18 Inhibits Hepatitis B Virus Replication in the Livers of Transgenic Mice

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2002 Oct 9

PMID 12368312

Citations 73

Authors

Kiminori Kimura

Kazuhiro Kakimi

Stefan Wieland

Luca G Guidotti

Francis V Chisari

Affiliations

Soon will be listed here.

Abstract

Interleukin-18 (IL-18) produced by activated antigen-presenting cells stimulates natural killer (NK) cells, natural killer T (NKT) cells, and T cells to secrete gamma interferon (IFN-gamma). In this study, injection of a single 10- micro g dose of recombinant murine IL-18 rapidly, reversibly, and noncytopathically inhibited hepatitis B virus (HBV) replication in the livers of HBV transgenic mice. Furthermore, HBV replication was inhibited by as little as 1 micro g of IL-18 injected repetitively, and also by a single 0.1- micro g dose of IL-18 injected together with 1 ng of IL-12, neither of which inhibited HBV replication individually, demonstrating synergy between these cytokines in this system. The antiviral effect of IL-18 was mediated by its ability to activate resident intrahepatic NK cells and NKT cells to produce IFN-gamma and by its ability to induce IFN-alpha/beta production in the liver. These results suggest that IL-18 has the potential to contribute to the control of HBV replication during self-limited infection and that it may have therapeutic value for the treatment of patients with chronic hepatitis.

Citing Articles

Many Ways to Communicate-Crosstalk between the HBV-Infected Cell and Its Environment.

Walter A, van de Klundert M, Jung S Pathogens. 2023; 12(1).

PMID: 36678377 PMC: 9866324. DOI: 10.3390/pathogens12010029.

New insights into iNKT cells and their roles in liver diseases.

Gu X, Chu Q, Ma X, Wang J, Chen C, Guan J Front Immunol. 2022; 13:1035950.

PMID: 36389715 PMC: 9643775. DOI: 10.3389/fimmu.2022.1035950.

Therapeutic Perspectives of IL1 Family Members in Liver Diseases: An Update.

Curcic I, Kizivat T, Petrovic A, Smolic R, Tabll A, Wu G J Clin Transl Hepatol. 2022; 10(6):1186-1193.

PMID: 36381097 PMC: 9634773. DOI: 10.14218/JCTH.2021.00501.

Toll-like receptor-mediated innate immunity orchestrates adaptive immune responses in HBV infection.

Du Y, Wu J, Liu J, Zheng X, Yang D, Lu M Front Immunol. 2022; 13:965018.

PMID: 35967443 PMC: 9372436. DOI: 10.3389/fimmu.2022.965018.

The efficacy of pegylated interferon alpha-2a and entecavir in HBeAg-positive children and adolescents with chronic hepatitis B.

He Y, Zhou Y, Wang H, Peng X, Chang Y, Hu P BMC Pediatr. 2022; 22(1):426.

PMID: 35854256 PMC: 9297582. DOI: 10.1186/s12887-022-03482-0.

References

Hameg A, Arnould A, Machavoine F, Koezuka Y, Schneider E, Herbelin A . A distinct IL-18-induced pathway to fully activate NK T lymphocytes independently from TCR engagement. J Immunol. 1999; 163(11):5871-6. View

Tsutsui H, Kayagaki N, Kuida K, Nakano H, Hayashi N, Takeda K . Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity. 1999; 11(3):359-67. DOI: 10.1016/s1074-7613(00)80111-9. View

Wieland S, Guidotti L, Chisari F . Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice. J Virol. 2001; 74(9):4165-73. PMC: 111931. DOI: 10.1128/jvi.74.9.4165-4173.2000. View

Tsutsui H, Matsui K, Okamura H, Nakanishi K . Pathophysiological roles of interleukin-18 in inflammatory liver diseases. Immunol Rev. 2000; 174:192-209. DOI: 10.1034/j.1600-0528.2002.017418.x. View

Kakimi K, Guidotti L, Koezuka Y, Chisari F . Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J Exp Med. 2000; 192(7):921-30. PMC: 2193313. DOI: 10.1084/jem.192.7.921. View

Pasquetto V, Guidotti L, Kakimi K, Tsuji M, Chisari F . Host-virus interactions during malaria infection in hepatitis B virus transgenic mice. J Exp Med. 2000; 192(4):529-36. PMC: 2193244. DOI: 10.1084/jem.192.4.529. View

Guidotti L, Chisari F . Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol. 2001; 19:65-91. DOI: 10.1146/annurev.immunol.19.1.65. View

Nakanishi K, Yoshimoto T, Tsutsui H, Okamura H . Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol. 2001; 19:423-74. DOI: 10.1146/annurev.immunol.19.1.423. View

Robek M, Wieland S, Chisari F . Inhibition of hepatitis B virus replication by interferon requires proteasome activity. J Virol. 2002; 76(7):3570-4. PMC: 136040. DOI: 10.1128/jvi.76.7.3570-3574.2002. View

10.

Pasquetto V, Wieland S, Uprichard S, Tripodi M, Chisari F . Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures. J Virol. 2002; 76(11):5646-53. PMC: 137053. DOI: 10.1128/jvi.76.11.5646-5653.2002. View

11.

Hobbs M, Weigle W, Noonan D, Torbett B, McEvilly R, Koch R . Patterns of cytokine gene expression by CD4+ T cells from young and old mice. J Immunol. 1993; 150(8 Pt 1):3602-14. View

12.

Tripp C, Gately M, Hakimi J, Ling P, UNANUE E . Neutralization of IL-12 decreases resistance to Listeria in SCID and C.B-17 mice. Reversal by IFN-gamma. J Immunol. 1994; 152(4):1883-7. View

13.

Muller U, Steinhoff U, Reis L, Hemmi S, Pavlovic J, Zinkernagel R . Functional role of type I and type II interferons in antiviral defense. Science. 1994; 264(5167):1918-21. DOI: 10.1126/science.8009221. View

14.

Guidotti L, Matzke B, Schaller H, Chisari F . High-level hepatitis B virus replication in transgenic mice. J Virol. 1995; 69(10):6158-69. PMC: 189513. DOI: 10.1128/JVI.69.10.6158-6169.1995. View

15.

Okamura H, Tsutsi H, Komatsu T, Yutsudo M, HAKURA A, Tanimoto T . Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 1995; 378(6552):88-91. DOI: 10.1038/378088a0. View

16.

Guidotti L, Ishikawa T, Hobbs M, Matzke B, Schreiber R, Chisari F . Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity. 1996; 4(1):25-36. DOI: 10.1016/s1074-7613(00)80295-2. View

17.

Cavanaugh V, Guidotti L, Chisari F . Interleukin-12 inhibits hepatitis B virus replication in transgenic mice. J Virol. 1997; 71(4):3236-43. PMC: 191456. DOI: 10.1128/JVI.71.4.3236-3243.1997. View

18.

Franco A, Guidotti L, Hobbs M, Pasquetto V, Chisari F . Pathogenetic effector function of CD4-positive T helper 1 cells in hepatitis B virus transgenic mice. J Immunol. 1997; 159(4):2001-8. View

19.

Cavanaugh V, Guidotti L, Chisari F . Inhibition of hepatitis B virus replication during adenovirus and cytomegalovirus infections in transgenic mice. J Virol. 1998; 72(4):2630-7. PMC: 109701. DOI: 10.1128/JVI.72.4.2630-2637.1998. View

20.

Dinarello C, Novick D, Puren A, Fantuzzi G, Shapiro L, Muhl H . Overview of interleukin-18: more than an interferon-gamma inducing factor. J Leukoc Biol. 1998; 63(6):658-64. View